Is MAP3K10 p.Ser775Cys (c.2324C>G) pathogenic?

MAP3K10 p.Ser775Cys (c.2324C>G) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely benign (0.0841); Low-frequency (popmax 2.24%, eas).

How common is MAP3K10 p.Ser775Cys (c.2324C>G) in the general population?

MAP3K10 p.Ser775Cys (c.2324C>G) is low-frequency (popmax 2.24%, eas) (gnomAD).

What do computational predictors say about MAP3K10 p.Ser775Cys (c.2324C>G)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

MAP3K10 p.Ser775Cys

c.2324C>G · rs1973296720 · VCV2361576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.24%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -9.00	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 3	GERP 0.33, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,345 bp · p 0.89 · regional, not allelic
Overall
CADD	22.3	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 2.24% East Asian · 776/34,608 alleles

Filtering AF 2.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.06%

Overall 0.56% 7,953/1,421,194 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.24%	45
Ashkenazi Jewishnot grpmax-eligible	1.36%	74
Finnishnot grpmax-eligible	1.08%	92
Remaining individualsnot grpmax-eligible	1.06%	95
Middle Eastern	1%	100
Admixed American	0.56%	179
European (non-Finnish)	0.48%	208
African / African-American	0.474%	211
South Asian	0.108%	929

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.Ser775Cys
Coding: c.2324C>G
MANE Select: NM_002446
dbSNP: rs1973296720
Type: single nucleotide variant
Location: chr19:40214003 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 775: the 'disordered' region

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

Similar variants

MAP3K10 p.Ser775Ala 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-ser775cys (accessed [today's date]).

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