Is ITGA7 p.Phe439= (c.1317C>T) pathogenic?

ITGA7 p.Phe439= (c.1317C>T) is classified Conflicting classifications of pathogenicity in ITGA7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0225%, nfe); Associated with congenital muscular dystrophy due to integrin alpha-7 deficiency.

What condition is associated with ITGA7 p.Phe439= (c.1317C>T)?

ITGA7 p.Phe439= (c.1317C>T) is associated with congenital muscular dystrophy due to integrin alpha-7 deficiency (ClinVar).

How common is ITGA7 p.Phe439= (c.1317C>T) in the general population?

ITGA7 p.Phe439= (c.1317C>T) is ultra-rare (popmax 0.0225%, nfe) (gnomAD).

ITGA7 p.Phe439=

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.1317C>T · rs200714716 · VCV199075

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, 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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -4.4	GERP -3.7
Overall
CADD	7.597	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0225% European (non-Finnish) · 265/1,180,020 alleles

Filtering AF 0.0202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.0188% 303/1,613,992 alleles · ultra-rare exomes 276/1,461,892 · genomes 27/152,100 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0328%	3,050
European (non-Finnish)grpmax	0.0225%	4,453
Remaining individualsnot grpmax-eligible	0.0112%	8,925
South Asian	0.00549%	18,216
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,441
East Asian	0.00223%	44,894
Admixed American	0.00167%	59,998

Finnish 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.Phe439=
Coding: c.1317C>T
MANE Select: NM_002206
dbSNP: rs200714716
Type: single nucleotide variant
Location: chr12:55697787 (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)

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ITGA7 p.Arg604Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg798Ter Pathogenic/Likely pathogenic ★★ same condition
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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-phe439 (accessed [today's date]).

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