Is COL1A2 p.Ala203Pro (c.607G>C) pathogenic?

COL1A2 p.Ala203Pro (c.607G>C) is classified Uncertain significance in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-04). AlphaMissense: likely benign (0.1614); Very rare (popmax 0.00167%, amr).

How common is COL1A2 p.Ala203Pro (c.607G>C) in the general population?

COL1A2 p.Ala203Pro (c.607G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about COL1A2 p.Ala203Pro (c.607G>C)?

AlphaMissense predicts likely benign (score 0.1614) — an in-silico prediction, not a clinical call.

COL1A2 p.Ala203Pro

c.607G>C · rs1198800868 · VCV432608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1614	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -7.32	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 6.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.09 · regional, not allelic
Overall
CADD	22.3	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 0.00167% Admixed American · 1/60,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,461,656 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.00017%	589,957

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.Ala203Pro
Coding: c.607G>C
MANE Select: NM_000089
dbSNP: rs1198800868
Type: single nucleotide variant
Location: chr7:94407859 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 203: the 'disordered' region

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

Similar variants

COL1A2 p.Ala203= Likely benign ★ same residue
COL1A2 c.1197+5G>A Pathogenic ★★ same type
COL1A2 c.1404+1G>A Pathogenic/Likely pathogenic ★★ same type
COL1A2 c.1503+1G>A Pathogenic/Likely pathogenic ★★ same type
COL1A2 c.1503+1G>C Pathogenic ★★ same type
COL1A2 c.1557+3A>G Pathogenic ★★ same type
COL1A2 c.1971+1G>A Pathogenic ★★ same type
COL1A2 c.1972-1G>T Likely pathogenic ★★ 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/col1a2-p-ala203pro (accessed [today's date]).

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