Is ITGA7 p.Pro188= (c.564C>T) pathogenic?

ITGA7 p.Pro188= (c.564C>T) is classified Likely benign in ITGA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). Very rare (popmax 0.000932%, nfe); Associated with congenital muscular dystrophy due to integrin alpha-7 deficiency.

What condition is associated with ITGA7 p.Pro188= (c.564C>T)?

ITGA7 p.Pro188= (c.564C>T) is associated with congenital muscular dystrophy due to integrin alpha-7 deficiency (ClinVar).

How common is ITGA7 p.Pro188= (c.564C>T) in the general population?

ITGA7 p.Pro188= (c.564C>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

ITGA7 p.Pro188=

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.564C>T · rs763955304 · VCV1553222

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

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 1.2	GERP -1.4, phastCons 1
Overall
CADD	8.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,046 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000867% 14/1,614,106 alleles · very rare exomes 10/1,461,892 · genomes 4/152,214 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,830
European (non-Finnish)grpmax	0.000932%	107,277

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro188=
Coding: c.564C>T
MANE Select: NM_002206
dbSNP: rs763955304
Type: single nucleotide variant
Location: chr12:55701005 (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.Pro188Leu 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-pro188 (accessed [today's date]).

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