Is COL7A1 p.Pro644Ser (c.1930C>T) pathogenic?

COL7A1 p.Pro644Ser (c.1930C>T) is classified Uncertain significance in COL7A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-27). AlphaMissense: likely benign (0.0617); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL7A1 p.Pro644Ser (c.1930C>T)?

COL7A1 p.Pro644Ser (c.1930C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL7A1 p.Pro644Ser (c.1930C>T) in the general population?

COL7A1 p.Pro644Ser (c.1930C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about COL7A1 p.Pro644Ser (c.1930C>T)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro644Ser

c.1930C>T · rs1384386683 · VCV1346022

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.091	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1	GERP -3.5
Regional constraint	o/e 0.84	unconstrained · MANE · 6,279 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	14.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 0.000657% 1/152,116 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.Pro644Ser
Coding: c.1930C>T
MANE Select: NM_000094
dbSNP: rs1384386683
Type: single nucleotide variant
Location: chr3:48590333 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 644: the 'nonhelical region (nc1)' region; the 'disordered' 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.Pro644= 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
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-pro644ser (accessed [today's date]).

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