Is COL1A2 p.Pro810Ser (c.2428C>T) pathogenic?

COL1A2 p.Pro810Ser (c.2428C>T) is classified Uncertain significance in COL1A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0578); Ultra-rare (popmax 0.0495%, mid).

How common is COL1A2 p.Pro810Ser (c.2428C>T) in the general population?

COL1A2 p.Pro810Ser (c.2428C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about COL1A2 p.Pro810Ser (c.2428C>T)?

AlphaMissense predicts likely benign (score 0.0578) — an in-silico prediction, not a clinical call.

COL1A2 p.Pro810Ser

c.2428C>T · rs779393490 · VCV585500

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0578 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0578	likely benign
REVEL	0.615	indeterminate
SaProt	LLR -8.01	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 0.27	GERP 0.34, phastCons 0.009
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	16.86	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.000274% 4/1,461,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Pro810Ser
Coding: c.2428C>T
MANE Select: NM_000089
dbSNP: rs779393490
Type: single nucleotide variant
Location: chr7:94422981 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 810: a UniProt-annotated variant site (in oi2); the 'disordered' region

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

Similar variants

COL1A2 p.Pro810Arg Uncertain significance ★ ⚠ 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-pro810ser (accessed [today's date]).

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