Is MAP3K10 p.Val68Met (c.202G>A) pathogenic?

MAP3K10 p.Val68Met (c.202G>A) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely pathogenic (0.6696); Very rare (popmax 0.00034%, nfe).

How common is MAP3K10 p.Val68Met (c.202G>A) in the general population?

MAP3K10 p.Val68Met (c.202G>A) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about MAP3K10 p.Val68Met (c.202G>A)?

AlphaMissense predicts likely pathogenic (score 0.6696) — an in-silico prediction, not a clinical call.

MAP3K10 p.Val68Met

c.202G>A · rs773826241 · VCV2227148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6696	likely pathogenic
REVEL	0.188	benign-leaning
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 9.4e-15 · regional, not allelic
Overall
CADD	29.6	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 0.00034% European (non-Finnish) · 4/1,177,244 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000344% 5/1,452,518 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00166%	60,186
European (non-Finnish)grpmax	0.00034%	294,311

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val68Met
Coding: c.202G>A
MANE Select: NM_002446
dbSNP: rs773826241
Type: single nucleotide variant
Location: chr19:40192233 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 68: the sh3 domain; a β-strand

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-val68met (accessed [today's date]).

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