Is ITGA7 p.Ser558= (c.1674G>A) pathogenic?

ITGA7 p.Ser558= (c.1674G>A) is classified Likely benign in ITGA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.00267%, afr); Associated with congenital muscular dystrophy due to integrin alpha-7 deficiency.

What condition is associated with ITGA7 p.Ser558= (c.1674G>A)?

ITGA7 p.Ser558= (c.1674G>A) is associated with congenital muscular dystrophy due to integrin alpha-7 deficiency (ClinVar).

How common is ITGA7 p.Ser558= (c.1674G>A) in the general population?

ITGA7 p.Ser558= (c.1674G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

ITGA7 p.Ser558=

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.1674G>A · rs967398275 · VCV2742495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

congenital muscular dystrophy due to integrin alpha-7 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.5	GERP -2.6
Overall
CADD	1.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,922 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,614,022 alleles · very rare exomes 6/1,461,816 · genomes 3/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,461
East Asian	0.00223%	44,896
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000424%	236,010

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.Ser558=
Coding: c.1674G>A
MANE Select: NM_002206
dbSNP: rs967398275
Type: single nucleotide variant
Location: chr12:55696962 (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.Ser558Leu Uncertain significance ★★ ⚠ 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
ITGA7 p.Gln76Ter 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-ser558 (accessed [today's date]).

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