Is MAP3K10 p.Arg39Ser (c.117G>C) pathogenic?

MAP3K10 p.Arg39Ser (c.117G>C) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.6293); Very rare (popmax 0.00681%, nfe).

How common is MAP3K10 p.Arg39Ser (c.117G>C) in the general population?

MAP3K10 p.Arg39Ser (c.117G>C) is very rare (popmax 0.00681%, nfe) (gnomAD).

What do computational predictors say about MAP3K10 p.Arg39Ser (c.117G>C)?

AlphaMissense predicts likely pathogenic (score 0.6293) — an in-silico prediction, not a clinical call.

MAP3K10 p.Arg39Ser

c.117G>C · rs757122193 · VCV2345966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00681%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6293	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -12.41	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.89, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 9.4e-15 · regional, not allelic
Overall
CADD	24.7	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 0.00681% European (non-Finnish) · 80/1,174,154 alleles

Filtering AF 0.00557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.00525% 84/1,598,880 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00681%	14,677
Remaining individualsnot grpmax-eligible	0.00323%	30,935
African / African-American	0.00268%	37,302

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.Arg39Ser
Coding: c.117G>C
MANE Select: NM_002446
dbSNP: rs757122193
Type: single nucleotide variant
Location: chr19:40192148 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 39: the sh3 domain

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-arg39ser (accessed [today's date]).

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