Is COL7A1 p.Ala172Val (c.515C>T) pathogenic?

COL7A1 p.Ala172Val (c.515C>T) is classified Conflicting classifications of pathogenicity in COL7A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: ambiguous (0.3435); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with COL7A1 p.Ala172Val (c.515C>T)?

COL7A1 p.Ala172Val (c.515C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL7A1 p.Ala172Val (c.515C>T) in the general population?

COL7A1 p.Ala172Val (c.515C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about COL7A1 p.Ala172Val (c.515C>T)?

AlphaMissense predicts ambiguous (score 0.3435) — an in-silico prediction, not a clinical call.

COL7A1 p.Ala172Val

c.515C>T · rs370740757 · VCV2042225

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3435 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3435	ambiguous
REVEL	0.645	pathogenic-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.7	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 6,279 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,884 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.0018% 29/1,613,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0304%	3,289
East Asiangrpmax	0.0156%	6,412
African / African-American	0.004%	24,971

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: COL7A1
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_000094
dbSNP: rs370740757
Type: single nucleotide variant
Location: chr3:48593361 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 172: the 'nonhelical region (nc1)' region; the vwfa 1 domain

Full COL7A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL7A1 p.Ala172= Likely benign ★ same residue
COL7A1 p.Ala1282Thr Uncertain significance ★★ ⚠ same condition
COL7A1 p.Ala2258Thr Uncertain significance ★★ ⚠ same condition
COL7A1 p.Ala2328Gly Uncertain significance ★★ same condition
COL7A1 p.Ala2513Val Uncertain significance ★★ ⚠ same condition
COL7A1 p.Ala2592Glu Uncertain significance ★★ same condition
COL7A1 p.Ala36Thr Uncertain significance ★★ same condition
COL7A1 p.Ala74Thr Uncertain significance ★★ ⚠ 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/col7a1-p-ala172val (accessed [today's date]).

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