Is MAP3K9 p.Pro1059Ser (c.3175C>T) pathogenic?

MAP3K9 p.Pro1059Ser (c.3175C>T) is classified Uncertain significance in MAP3K9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely benign (0.0628); Absent from gnomAD v4.1.

How common is MAP3K9 p.Pro1059Ser (c.3175C>T) in the general population?

MAP3K9 p.Pro1059Ser (c.3175C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K9 p.Pro1059Ser (c.3175C>T)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

MAP3K9 p.Pro1059Ser

c.3175C>T · VCV3293101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.28	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 0.82	GERP -2.1, phastCons 0.9
Regional constraint	o/e 0.98	unconstrained · MANE · 2,665 bp · p 0.69 · regional, not allelic
Overall
CADD	7.437	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: MAP3K9
Protein: p.Pro1059Ser
Coding: c.3175C>T
MANE Select: NM_001284230
Type: single nucleotide variant
Location: chr14:70730520 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.56 · 2 PDB

Full MAP3K9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K9 p.Pro1059Leu Uncertain significance ★ ⚠ same residue
MAP3K9 c.2027-415G>T Uncertain significance ★ same type
MAP3K9 p.Ala1086Ser Uncertain significance ★ ⚠ same type
MAP3K9 p.Ala116Gly Uncertain significance ★ ⚠ same type
MAP3K9 p.Ala246Thr Uncertain significance ★ ⚠ same type
MAP3K9 p.Ala309Val Uncertain significance ★ same type
MAP3K9 p.Ala379Thr Uncertain significance ★ ⚠ same type
MAP3K9 p.Ala65Ser 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/map3k9-p-pro1059ser (accessed [today's date]).

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