Is COL7A1 p.Arg910Trp (c.2728C>T) pathogenic?

COL7A1 p.Arg910Trp (c.2728C>T) is classified Conflicting classifications of pathogenicity in COL7A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-04). AlphaMissense: likely benign (0.0934); Very rare (popmax 0.0094%, afr); Associated with Inborn genetic diseases.

What condition is associated with COL7A1 p.Arg910Trp (c.2728C>T)?

COL7A1 p.Arg910Trp (c.2728C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL7A1 p.Arg910Trp (c.2728C>T) in the general population?

COL7A1 p.Arg910Trp (c.2728C>T) is very rare (popmax 0.0094%, afr) (gnomAD).

What do computational predictors say about COL7A1 p.Arg910Trp (c.2728C>T)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

COL7A1 p.Arg910Trp

c.2728C>T · rs751815309 · VCV2419451

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0094%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.125	moderately 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 2.1	GERP -1.3, phastCons 0.93
Regional constraint	o/e 1.04	unconstrained · MANE · 2,281 bp · p 0.43 · regional, not allelic
Overall
CADD	24.4	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 0.0094% African / African-American · 7/74,506 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00106% 17/1,598,258 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0094%	10,644
East Asian	0.00455%	21,980
Remaining individualsnot grpmax-eligible	0.00323%	30,936
Admixed American	0.00173%	57,652
South Asian	0.00112%	89,070
European (non-Finnish)	0.000341%	293,245

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.Arg910Trp
Coding: c.2728C>T
MANE Select: NM_000094
dbSNP: rs751815309
Type: single nucleotide variant
Location: chr3:48587922 (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

Disease context

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

Similar variants

COL7A1 p.Arg910Leu Uncertain significance ★★ ⚠ same residue
COL7A1 p.Arg910Pro Uncertain significance ★★ same residue
COL7A1 p.Arg910= Likely benign ★ same residue
COL7A1 p.Arg910Gln 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

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-arg910trp (accessed [today's date]).

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