Is COL6A5 p.Val2425Ile (c.7273G>A) pathogenic?

COL6A5 p.Val2425Ile (c.7273G>A) is classified Benign in COL6A5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-08-03). AlphaMissense: likely benign (0.0729); Common (popmax 6.21%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about COL6A5 p.Val2425Ile (c.7273G>A)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

COL6A5 p.Val2425Ile

Q: How common is COL6A5 p.Val2425Ile (c.7273G>A) in the general population?

COL6A5 p.Val2425Ile (c.7273G>A) is common (popmax 6.21%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7273G>A · rs75328271 · VCV781841

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.21%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -1.6, phastCons 0.002
Overall
CADD	8.871	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 6.21% African / African-American · 4,657/74,946 alleles

Filtering AF 6.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 6%

Overall 0.557% 8,992/1,612,960 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.21%	16
Middle Eastern	2.23%	45
South Asian	1.82%	55
Ashkenazi Jewishnot grpmax-eligible	1.21%	83
Remaining individualsnot grpmax-eligible	0.796%	126
Admixed American	0.553%	181
European (non-Finnish)	0.113%	883
Finnishnot grpmax-eligible	0.0328%	3,046
East Asian	0.00446%	22,408

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: COL6A5
Protein: p.Val2425Ile
Coding: c.7273G>A
MANE Select: NM_001278298
dbSNP: rs75328271
Type: single nucleotide variant
Location: chr3:130469277 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 70.94
Residue 2425: the vwfa 10 domain; the 'nonhelical region' region

Full COL6A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL6A5 p.Ala2589Thr Benign ★★ same type
COL6A5 p.Asn641His Benign ★★ same type
COL6A5 p.Asp160= Benign ★★ same type
COL6A5 p.Glu2272Ter Benign ★★ same type
COL6A5 p.Lys620= Benign ★★ same type
COL6A5 p.Ser1539Thr Benign ★★ same type
COL6A5 p.Thr572= Benign ★★ same type
COL6A5 p.Val669Gly Likely benign ★★ 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/col6a5-p-val2425ile (accessed [today's date]).

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