Is MAP3K9 p.Pro811Arg (c.2432C>G) pathogenic?

MAP3K9 p.Pro811Arg (c.2432C>G) is classified Uncertain significance in MAP3K9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.7064); Ultra-rare (popmax 0.0285%, sas).

How common is MAP3K9 p.Pro811Arg (c.2432C>G) in the general population?

MAP3K9 p.Pro811Arg (c.2432C>G) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

What do computational predictors say about MAP3K9 p.Pro811Arg (c.2432C>G)?

AlphaMissense predicts likely pathogenic (score 0.7064) — an in-silico prediction, not a clinical call.

MAP3K9 p.Pro811Arg

c.2432C>G · VCV3542919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7064 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7064	likely pathogenic
REVEL	0.675	pathogenic-leaning
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,665 bp · p 0.69 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% South Asian · 26/91,076 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00186% 30/1,613,918 alleles · ultra-rare exomes 28/1,461,792 · genomes 2/152,126 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
European (non-Finnish)	0.000339%	294,986

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.Pro811Arg
Coding: c.2432C>G
MANE Select: NM_001284230
Type: single nucleotide variant
Location: chr14:70732937 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.56 · 2 PDB
Residue 811: the 'disordered' region

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

Similar variants

MAP3K9 p.Pro811Gln 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-pro811arg (accessed [today's date]).

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