Is COL6A5 p.Pro1502His (c.4505C>A) pathogenic?

COL6A5 p.Pro1502His (c.4505C>A) is classified Uncertain significance in COL6A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.1346); Ultra-rare (popmax 0.044%, afr).

How common is COL6A5 p.Pro1502His (c.4505C>A) in the general population?

COL6A5 p.Pro1502His (c.4505C>A) is ultra-rare (popmax 0.044%, afr) (gnomAD).

What do computational predictors say about COL6A5 p.Pro1502His (c.4505C>A)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

COL6A5 p.Pro1502His

c.4505C>A · rs772303994 · VCV2378144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 2, phastCons 0.96
Overall
CADD	22.4	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 0.044% African / African-American · 32/72,738 alleles

Filtering AF 0.0319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00239% 37/1,547,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.044%	2,273
Middle Eastern	0.0167%	5,974
Remaining individualsnot grpmax-eligible	0.00501%	19,951
Admixed American	0.00199%	50,268

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.Pro1502His
Coding: c.4505C>A
MANE Select: NM_001278298
dbSNP: rs772303994
Type: single nucleotide variant
Location: chr3:130409351 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 70.94
Residue 1502: the collagen-like 3 domain; the 'triple-helical region' region; the 'disordered' 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.Val2425Ile 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-pro1502his (accessed [today's date]).

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