Is MAP3K10 p.Phe95Leu (c.285C>A) pathogenic?

MAP3K10 p.Phe95Leu (c.285C>A) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely pathogenic (0.9964); Very rare (popmax 0.00289%, nfe).

How common is MAP3K10 p.Phe95Leu (c.285C>A) in the general population?

MAP3K10 p.Phe95Leu (c.285C>A) is very rare (popmax 0.00289%, nfe) (gnomAD).

What do computational predictors say about MAP3K10 p.Phe95Leu (c.285C>A)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

MAP3K10 p.Phe95Leu

c.285C>A · rs1341869847 · VCV3122829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00289%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 6% in MAP3K10
REVEL	0.451	indeterminate
SaProt	LLR -9.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 9.4e-15 · regional, not allelic
Overall
CADD	24.5	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 0.00289% European (non-Finnish) · 34/1,177,944 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00247% 36/1,455,690 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00289%	34,645
Remaining individualsnot grpmax-eligible	0.00161%	62,252
South Asian	0.0011%	90,570

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.Phe95Leu
Coding: c.285C>A
MANE Select: NM_002446
dbSNP: rs1341869847
Type: single nucleotide variant
Location: chr19:40192316 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB

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

Similar variants

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
MAP3K10 p.Ala661Thr 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-phe95leu (accessed [today's date]).

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