Is ITGA7 p.Arg287Cys (c.859C>T) pathogenic?

ITGA7 p.Arg287Cys (c.859C>T) is classified Uncertain significance in ITGA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.8751); Very rare (popmax 0.00833%, amr); Associated with congenital muscular dystrophy due to integrin alpha-7 deficiency.

What condition is associated with ITGA7 p.Arg287Cys (c.859C>T)?

ITGA7 p.Arg287Cys (c.859C>T) is associated with congenital muscular dystrophy due to integrin alpha-7 deficiency (ClinVar).

How common is ITGA7 p.Arg287Cys (c.859C>T) in the general population?

ITGA7 p.Arg287Cys (c.859C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about ITGA7 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely pathogenic (score 0.8751) — an in-silico prediction, not a clinical call.

ITGA7 p.Arg287Cys

Q: How is Congenital muscular dystrophy with integrin alpha-7 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.859C>T · rs563941470 · VCV1498394

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital muscular dystrophy due to integrin alpha-7 deficiency

Computational evidence

Protein change
AlphaMissense	0.8751	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -13.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.029 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R331C vs ClinVar R287C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,012 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00149% 24/1,613,632 alleles · very rare exomes 17/1,461,384 · genomes 7/152,248 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
South Asian	0.00439%	22,769
African / African-American	0.004%	25,007
Remaining individualsnot grpmax-eligible	0.0032%	31,222
Finnishnot grpmax-eligible	0.00157%	63,706
European (non-Finnish)	0.000763%	131,102

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ITGA7
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_002206
dbSNP: rs563941470
Type: single nucleotide variant
Location: chr12:55698849 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.14

Full ITGA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital muscular dystrophy due to integrin alpha-7 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital muscular dystrophy with integrin alpha-7 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ITGA7 p.Arg287Ser Uncertain significance ★★ ⚠ same residue
ITGA7 p.Arg287= Likely benign ★ same residue
ITGA7 c.1887+2T>C Likely pathogenic ★★ same condition
ITGA7 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg149Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg569Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg604Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg798Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/itga7-p-arg287cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown