Is COL7A1 p.Arg78Cys (c.232C>T) pathogenic?

COL7A1 p.Arg78Cys (c.232C>T) is classified Uncertain significance in COL7A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: ambiguous (0.4439); Very rare (popmax 0.00446%, eas).

How common is COL7A1 p.Arg78Cys (c.232C>T) in the general population?

COL7A1 p.Arg78Cys (c.232C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about COL7A1 p.Arg78Cys (c.232C>T)?

AlphaMissense predicts ambiguous (score 0.4439) — an in-silico prediction, not a clinical call.

COL7A1 p.Arg78Cys

c.232C>T · VCV3704976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
AlphaMissense	0.4439	ambiguous
REVEL	0.83	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 6,279 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	33.0	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 0.00446% East Asian · 2/44,882 alleles

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

Overall 0.000372% 6/1,611,522 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
South Asian	0.0033%	30,333
Admixed American	0.00167%	60,028

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.Arg78Cys
Coding: c.232C>T
MANE Select: NM_000094
Type: single nucleotide variant
Location: chr3:48594402 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 78: the 'nonhelical region (nc1)' region; the vwfa 1 domain

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

Similar variants

COL7A1 p.Arg78fs Likely 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
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
COL7A1 c.266+1G>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-arg78cys (accessed [today's date]).

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