Is COL7A1 p.Pro1805Ser (c.5413C>T) pathogenic?

COL7A1 p.Pro1805Ser (c.5413C>T) is classified Uncertain significance in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1231); Very rare (popmax 0.00223%, eas).

How common is COL7A1 p.Pro1805Ser (c.5413C>T) in the general population?

COL7A1 p.Pro1805Ser (c.5413C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COL7A1 p.Pro1805Ser (c.5413C>T)?

AlphaMissense predicts likely benign (score 0.1231) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro1805Ser

c.5413C>T · rs2107694745 · VCV1686592

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.1231	likely benign
REVEL	0.499	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	25.6	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 0.00223% East Asian · 1/44,888 alleles

Overall 0.000137% 2/1,461,662 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
European (non-Finnish)	8.47e-05%	1,179,949

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.Pro1805Ser
Coding: c.5413C>T
MANE Select: NM_000094
dbSNP: rs2107694745
Type: single nucleotide variant
Location: chr3:48578930 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 1805: the 'disordered' region; the 'triple-helical region' region

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

Similar variants

COL7A1 p.Pro1805Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
COL7A1 p.Pro1805= 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

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-pro1805ser (accessed [today's date]).

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