Is COL7A1 p.Pro141Ser (c.421C>T) pathogenic?

COL7A1 p.Pro141Ser (c.421C>T) is classified Uncertain significance in COL7A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). AlphaMissense: likely benign (0.1646); Very rare (popmax 0.000508%, nfe).

How common is COL7A1 p.Pro141Ser (c.421C>T) in the general population?

COL7A1 p.Pro141Ser (c.421C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about COL7A1 p.Pro141Ser (c.421C>T)?

AlphaMissense predicts likely benign (score 0.1646) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro141Ser

c.421C>T · VCV3618922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1646	likely benign
REVEL	0.659	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.64, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 6,279 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	21.8	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 0.000508% European (non-Finnish) · 6/1,180,028 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,864 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.Pro141Ser
Coding: c.421C>T
MANE Select: NM_000094
Type: single nucleotide variant
Location: chr3:48593542 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 141: 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.Pro141= 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
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-pro141ser (accessed [today's date]).

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