Is MAP3K9 p.Pro550Ser (c.1648C>T) pathogenic?

MAP3K9 p.Pro550Ser (c.1648C>T) is classified Uncertain significance in MAP3K9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: ambiguous (0.4288); Very rare (popmax 0.00333%, amr).

How common is MAP3K9 p.Pro550Ser (c.1648C>T) in the general population?

MAP3K9 p.Pro550Ser (c.1648C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MAP3K9 p.Pro550Ser (c.1648C>T)?

AlphaMissense predicts ambiguous (score 0.4288) — an in-silico prediction, not a clinical call.

MAP3K9 p.Pro550Ser

c.1648C>T · VCV3870271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4288	ambiguous
REVEL	0.269	benign-leaning
SaProt	LLR -6.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 16 kb · p 0.049 · regional, not allelic
Overall
CADD	27.0	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 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,614,064 alleles · very rare exomes 6/1,461,886 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,995
European (non-Finnish)	0.000593%	168,577

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.Pro550Ser
Coding: c.1648C>T
MANE Select: NM_001284230
Type: single nucleotide variant
Location: chr14:70740084 (GRCh38)
Gene constraint: LOEUF 0.674 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.56 · 2 PDB
Residue 550: the 'disordered' region

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

Similar variants

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MAP3K9 p.Ala246Thr Uncertain significance ★ ⚠ same type
MAP3K9 p.Ala309Val Uncertain significance ★ same type
MAP3K9 p.Ala379Thr Uncertain significance ★ ⚠ same type
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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-pro550ser (accessed [today's date]).

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