Is COL7A1 p.Ala2810Pro (c.8428G>C) pathogenic?

COL7A1 p.Ala2810Pro (c.8428G>C) is classified Uncertain significance in COL7A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.0033%, sas).

How common is COL7A1 p.Ala2810Pro (c.8428G>C) in the general population?

COL7A1 p.Ala2810Pro (c.8428G>C) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about COL7A1 p.Ala2810Pro (c.8428G>C)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

COL7A1 p.Ala2810Pro

c.8428G>C · VCV4687550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.222	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.43, phastCons 0.88
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	19.37	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,008 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,613,750 alleles · very rare

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.Ala2810Pro
Coding: c.8428G>C
MANE Select: NM_000094
Type: single nucleotide variant
Location: chr3:48565648 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 2810: the 'nonhelical region (nc2)' region

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

Similar variants

COL7A1 p.Ala2810Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
COL7A1 p.Ala2810= Likely benign ★ same residue
COL7A1 c.1240+1G>T Likely pathogenic ★★ same type
COL7A1 c.1637-1G>A Pathogenic/Likely pathogenic ★★ same type
COL7A1 c.1906+1G>T Likely pathogenic ★★ same type
COL7A1 c.2171-2A>G Likely pathogenic ★★ same type
COL7A1 c.2587+1G>A Pathogenic/Likely pathogenic ★★ same type
COL7A1 c.2587+40G>A Pathogenic/Likely pathogenic ★★ same type

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-ala2810pro (accessed [today's date]).

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