Is MAP3K15 p.Ala968Val (c.2903C>T) pathogenic?

MAP3K15 p.Ala968Val (c.2903C>T) is classified Uncertain significance in MAP3K15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0679); Rare (popmax 0.167%, mid).

How common is MAP3K15 p.Ala968Val (c.2903C>T) in the general population?

MAP3K15 p.Ala968Val (c.2903C>T) is rare (popmax 0.167%, mid) (gnomAD).

What do computational predictors say about MAP3K15 p.Ala968Val (c.2903C>T)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

MAP3K15 p.Ala968Val

c.2903C>T · VCV4103261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.3	GERP -3.4
Regional constraint	o/e 1.15	unconstrained · MANE · 155 kb · p 7.9e-07 · regional, not allelic
Overall
CADD	0.027	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 0.167% Middle Eastern · 7/4,187 alleles

Filtering AF 0.0784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0556%

Overall 0.0165% 193/1,172,265 alleles · rare exomes 179/1,060,221 · genomes 14/112,044 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.167%	598
Admixed American	0.0717%	1,394
Remaining individualsnot grpmax-eligible	0.0238%	4,198
European (non-Finnish)	0.0161%	6,213
South Asian	0.00566%	17,663
Ashkenazi Jewishnot grpmax-eligible	0.00469%	21,325
East Asian	0.00317%	31,501
African / African-American	0.00177%	56,397

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: MAP3K15
Protein: p.Ala968Val
Coding: c.2903C>T
MANE Select: NM_001001671
Type: single nucleotide variant
Location: chrX:19373566 (GRCh38)
Structure: AlphaFold pLDDT 75.41 · 1 PDB

Full MAP3K15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K15 p.Ala859Thr Uncertain significance ★★ ⚠ same type
MAP3K15 p.Ile295Ser Uncertain significance ★★ ⚠ same type
MAP3K15 p.Leu154Phe Uncertain significance ★★ ⚠ same type
MAP3K15 p.Thr1229Arg Uncertain significance ★★ ⚠ same type
MAP3K15 p.Ser199Asn Benign ★★ same type
MAP3K15 p.Val455Ile Likely benign ★★ same type
PDHA1 c.*1013C>A Benign ★★ same type
PDHA1 c.*1059G>A Benign ★★ 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/map3k15-p-ala968val (accessed [today's date]).

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