Is COL6A5 p.Asp2003Ala (c.6008A>C) pathogenic?

COL6A5 p.Asp2003Ala (c.6008A>C) is classified Uncertain significance in COL6A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0935); Ultra-rare (popmax 0.0527%, sas).

How common is COL6A5 p.Asp2003Ala (c.6008A>C) in the general population?

COL6A5 p.Asp2003Ala (c.6008A>C) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

What do computational predictors say about COL6A5 p.Asp2003Ala (c.6008A>C)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

COL6A5 p.Asp2003Ala

c.6008A>C · rs369112375 · VCV2363989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -5.58	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 -0.79	GERP -4.7
Overall
CADD	0.112	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 0.0527% South Asian · 48/91,064 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00576% 93/1,613,420 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0527%	1,897
Remaining individualsnot grpmax-eligible	0.0256%	3,903
East Asian	0.0224%	4,474
African / African-American	0.0213%	4,688
Admixed American	0.00167%	59,912
European (non-Finnish)	0.00017%	589,842

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.Asp2003Ala
Coding: c.6008A>C
MANE Select: NM_001278298
dbSNP: rs369112375
Type: single nucleotide variant
Location: chr3:130440346 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 70.94
Residue 2003: the vwfa 9 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.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-asp2003ala (accessed [today's date]).

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