Is COL1A2 p.Ala737Val (c.2210C>T) pathogenic?

COL1A2 p.Ala737Val (c.2210C>T) is classified Uncertain significance in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-11). AlphaMissense: likely benign (0.0729); Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with COL1A2 p.Ala737Val (c.2210C>T)?

COL1A2 p.Ala737Val (c.2210C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is COL1A2 p.Ala737Val (c.2210C>T) in the general population?

COL1A2 p.Ala737Val (c.2210C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about COL1A2 p.Ala737Val (c.2210C>T)?

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

COL1A2 p.Ala737Val

c.2210C>T · VCV3495238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.416	indeterminate
SaProt	LLR -6.87	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 4.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	21.7	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) · 1/1,179,966 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: COL1A2
Protein: p.Ala737Val
Coding: c.2210C>T
MANE Select: NM_000089
Type: single nucleotide variant
Location: chr7:94420563 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 737: a UniProt-annotated variant site (in oi2); the 'disordered' region

Full COL1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A2 c.2565+1G>A Pathogenic ★★ same condition
COL1A2 p.Ala1119Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL1A2 p.Gly259Ser Pathogenic/Likely pathogenic ★★ same condition
COL1A2 p.Gly907Ser Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.1251+2T>G Uncertain significance ★★ same condition
COL1A2 c.1404+4A>C Uncertain significance ★★ same condition
COL1A2 c.792+4A>T Uncertain significance ★★ same condition
COL1A2 p.Ala1035Thr 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/col1a2-p-ala737val (accessed [today's date]).

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