Is MAP3K15 p.Pro804Ala (c.2410C>G) pathogenic?

MAP3K15 p.Pro804Ala (c.2410C>G) is classified Uncertain significance in MAP3K15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.3187); Absent from gnomAD v4.1.

How common is MAP3K15 p.Pro804Ala (c.2410C>G) in the general population?

MAP3K15 p.Pro804Ala (c.2410C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K15 p.Pro804Ala (c.2410C>G)?

AlphaMissense predicts likely benign (score 0.3187) — an in-silico prediction, not a clinical call.

MAP3K15 p.Pro804Ala

c.2410C>G · VCV4103281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3187 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3187	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -8.32	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 1.3	GERP -0.36, phastCons 0.9
Regional constraint	o/e 1.15	unconstrained · MANE · 155 kb · p 7.9e-07 · regional, not allelic
Overall
CADD	14.29	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K15
Protein: p.Pro804Ala
Coding: c.2410C>G
MANE Select: NM_001001671
Type: single nucleotide variant
Location: chrX:19392023 (GRCh38)
Structure: AlphaFold pLDDT 75.41 · 1 PDB
Residue 804: the protein kinase domain

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-pro804ala (accessed [today's date]).

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