Is COL7A1 p.Arg613Gln (c.1838G>A) pathogenic?

COL7A1 p.Arg613Gln (c.1838G>A) is classified Conflicting classifications of pathogenicity in COL7A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-03). AlphaMissense: likely benign (0.0946); Ultra-rare (popmax 0.0134%, afr); Associated with Inborn genetic diseases.

What condition is associated with COL7A1 p.Arg613Gln (c.1838G>A)?

COL7A1 p.Arg613Gln (c.1838G>A) is associated with Inborn genetic diseases (ClinVar).

How common is COL7A1 p.Arg613Gln (c.1838G>A) in the general population?

COL7A1 p.Arg613Gln (c.1838G>A) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about COL7A1 p.Arg613Gln (c.1838G>A)?

AlphaMissense predicts likely benign (score 0.0946) — an in-silico prediction, not a clinical call.

COL7A1 p.Arg613Gln

c.1838G>A · rs774927826 · VCV1416776

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0946 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0946	likely benign
REVEL	0.1	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 3.2	GERP 1.1, phastCons 0.94
Regional constraint	o/e 0.84	unconstrained · MANE · 6,279 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	17.24	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 0.0134% African / African-American · 10/74,894 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000805% 13/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,489
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,026

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.Arg613Gln
Coding: c.1838G>A
MANE Select: NM_000094
dbSNP: rs774927826
Type: single nucleotide variant
Location: chr3:48590527 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 613: the 'nonhelical region (nc1)' region; the fibronectin type-iii 5 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.Arg613Ter Pathogenic/Likely pathogenic ★★ 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-arg613gln (accessed [today's date]).

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