Is COL7A1 p.Arg910Pro (c.2729G>C) pathogenic?

COL7A1 p.Arg910Pro (c.2729G>C) is classified Uncertain significance in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). AlphaMissense: ambiguous (0.4429); Very rare (popmax 0.00213%, nfe).

How common is COL7A1 p.Arg910Pro (c.2729G>C) in the general population?

COL7A1 p.Arg910Pro (c.2729G>C) is very rare (popmax 0.00213%, nfe) (gnomAD).

What do computational predictors say about COL7A1 p.Arg910Pro (c.2729G>C)?

AlphaMissense predicts ambiguous (score 0.4429) — an in-silico prediction, not a clinical call.

COL7A1 p.Arg910Pro

c.2729G>C · rs373718618 · VCV1303131

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00213%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4429	ambiguous
REVEL	0.303	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -4.2
Regional constraint	o/e 1.04	unconstrained · MANE · 2,281 bp · p 0.43 · regional, not allelic
Overall
CADD	17.66	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 0.00213% European (non-Finnish) · 25/1,173,136 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00124%

Overall 0.00156% 25/1,598,432 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.Arg910Pro
Coding: c.2729G>C
MANE Select: NM_000094
dbSNP: rs373718618
Type: single nucleotide variant
Location: chr3:48587921 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 910: the fibronectin type-iii 8 domain; the 'nonhelical region (nc1)' region

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

Similar variants

COL7A1 p.Arg910Leu Uncertain significance ★★ ⚠ same residue
COL7A1 p.Arg910Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
COL7A1 p.Arg910= Likely benign ★ same residue
COL7A1 p.Arg910Gln Likely benign ★ same residue
COL7A1 p.Arg910fs Pathogenic ★ 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

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-arg910pro (accessed [today's date]).

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