Is MAP3K9 p.Pro177= (c.531T>C) pathogenic?

MAP3K9 p.Pro177= (c.531T>C) is classified Likely benign in MAP3K9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Very rare (popmax 0.00878%, sas).

How common is MAP3K9 p.Pro177= (c.531T>C) in the general population?

MAP3K9 p.Pro177= (c.531T>C) is very rare (popmax 0.00878%, sas) (gnomAD).

MAP3K9 p.Pro177=

c.531T>C · rs769987149 · VCV2644345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.2
Overall
CADD	0.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,086 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000496% 8/1,614,180 alleles · very rare exomes 8/1,461,894 · genomes 0/152,286 · joint denominator

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: MAP3K9
Protein: p.Pro177=
Coding: c.531T>C
MANE Select: NM_001284230
dbSNP: rs769987149
Type: single nucleotide variant
Location: chr14:70800956 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.56 · 2 PDB
Residue 177: the protein kinase domain

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

Similar variants

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
MAP3K9 p.Ala787Val 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-pro177 (accessed [today's date]).

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