Is COL2A1 p.Lys262Arg (c.785A>G) pathogenic?

COL2A1 p.Lys262Arg (c.785A>G) is classified Conflicting classifications of pathogenicity in COL2A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0792); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with COL2A1 p.Lys262Arg (c.785A>G)?

COL2A1 p.Lys262Arg (c.785A>G) is associated with Inborn genetic diseases, Stickler syndrome, type I, nonsyndromic ocular (ClinVar).

How common is COL2A1 p.Lys262Arg (c.785A>G) in the general population?

COL2A1 p.Lys262Arg (c.785A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about COL2A1 p.Lys262Arg (c.785A>G)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

COL2A1 p.Lys262Arg

c.785A>G · rs769679774 · VCV1914047

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.46	indeterminate
SaProt	LLR -6.70	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 5.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 21 kb · p 2.4e-45 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000274% 4/1,461,704 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,010
European (non-Finnish)	0.000169%	590,009

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: COL2A1
Protein: p.Lys262Arg
Coding: c.785A>G
MANE Select: NM_001844
dbSNP: rs769679774
Type: single nucleotide variant
Location: chr12:47994455 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 262: the 'disordered' region; the 'triple-helical region' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Stickler syndrome, type I, nonsyndromic ocular

Similar variants

COL2A1 p.Lys262Asn Uncertain significance ★ same residue
COL2A1 c.1420-1G>A Pathogenic ★★ same condition
COL2A1 c.1527+1G>A Likely pathogenic ★★ same condition
COL2A1 p.Ala302Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL2A1 p.Arg565Cys Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Arg653Ter Pathogenic ★★ same condition
COL2A1 p.Arg785Ter Pathogenic ★★ same condition
COL2A1 p.Arg887Ter Pathogenic/Likely pathogenic ★★ 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/col2a1-p-lys262arg (accessed [today's date]).

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