Is IDH1 p.Ser287Cys (c.860C>G) pathogenic?

IDH1 p.Ser287Cys (c.860C>G) is classified Uncertain significance in IDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely pathogenic (0.8998); Absent from gnomAD v4.1.

How common is IDH1 p.Ser287Cys (c.860C>G) in the general population?

IDH1 p.Ser287Cys (c.860C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IDH1 p.Ser287Cys (c.860C>G)?

AlphaMissense predicts likely pathogenic (score 0.8998) — an in-silico prediction, not a clinical call.

IDH1 p.Ser287Cys

c.860C>G · rs2469016407 · VCV2491862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8998	likely pathogenic
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -11.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 3e-05 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IDH1
Protein: p.Ser287Cys
Coding: c.860C>G
MANE Select: NM_005896
dbSNP: rs2469016407
Type: single nucleotide variant
Location: chr2:208239994 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 64 PDB

Full IDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IDH1 p.Arg132Cys Pathogenic/Likely pathogenic ★★ same type
IDH1 p.Arg132His Pathogenic/Likely pathogenic ★★ same type
IDH1 p.Arg317His Uncertain significance ★★ ⚠ same type
IDH1 p.Asp38Asn Uncertain significance ★★ ⚠ same type
IDH1 p.Met318Thr Uncertain significance ★★ ⚠ same type
IDH1 c.122+105G>A Benign ★★ same type
IDH1 c.123-4C>T Benign ★★ same type
IDH1 c.415-238A>G 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/idh1-p-ser287cys (accessed [today's date]).

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