Is ITGA7 p.Pro553= (c.1659C>G) pathogenic?

ITGA7 p.Pro553= (c.1659C>G) is classified Benign/Likely benign in ITGA7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.832%, mid); Associated with congenital muscular dystrophy due to integrin alpha-7 deficiency.

What condition is associated with ITGA7 p.Pro553= (c.1659C>G)?

ITGA7 p.Pro553= (c.1659C>G) is associated with congenital muscular dystrophy due to integrin alpha-7 deficiency (ClinVar).

How common is ITGA7 p.Pro553= (c.1659C>G) in the general population?

ITGA7 p.Pro553= (c.1659C>G) is rare (popmax 0.832%, mid) (gnomAD).

ITGA7 p.Pro553=

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.1659C>G · rs144052152 · VCV94033

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.832%, mid)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -1.8, phastCons 0.96
Overall
CADD	6.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.832% Middle Eastern · 50/6,008 alleles

Filtering AF 0.649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.583%

Overall 0.121% 1,954/1,614,134 alleles · rare exomes 1,818/1,461,814 · genomes 136/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.832%	120
South Asian	0.483%	207
Remaining individualsnot grpmax-eligible	0.171%	584
European (non-Finnish)	0.108%	929
Admixed American	0.095%	1,053
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935
African / African-American	0.0173%	5,773
Finnishnot grpmax-eligible	0.0156%	6,404
East Asian	0.00223%	44,882

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.Pro553=
Coding: c.1659C>G
MANE Select: NM_002206
dbSNP: rs144052152
Type: single nucleotide variant
Location: chr12:55696977 (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

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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
ITGA7 p.Gln83Ter 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-pro553 (accessed [today's date]).

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