Is MAP3K10 p.Arg495Trp (c.1483C>T) pathogenic?

MAP3K10 p.Arg495Trp (c.1483C>T) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.2706); Very rare (popmax 0.00223%, eas).

How common is MAP3K10 p.Arg495Trp (c.1483C>T) in the general population?

MAP3K10 p.Arg495Trp (c.1483C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MAP3K10 p.Arg495Trp (c.1483C>T)?

AlphaMissense predicts likely benign (score 0.2706) — an in-silico prediction, not a clinical call.

MAP3K10 p.Arg495Trp

c.1483C>T · rs1430392363 · VCV2291978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2706	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 9.4e-15 · regional, not allelic
Overall
CADD	27.5	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00041% 6/1,461,836 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Admixed American	0.00167%	60,024
South Asian	0.0011%	91,086
European (non-Finnish)	0.000254%	393,335

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: MAP3K10
Protein: p.Arg495Trp
Coding: c.1483C>T
MANE Select: NM_002446
dbSNP: rs1430392363
Type: single nucleotide variant
Location: chr19:40209150 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 495: the 'disordered' region

Full MAP3K10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K10 p.Arg495Gln Uncertain significance ★ ⚠ same residue
MAP3K10 p.Ala240Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala263Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala364Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala488Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala603Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala648Val Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala658Thr Uncertain significance ★ ⚠ 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/map3k10-p-arg495trp (accessed [today's date]).

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