Is MAP3K7 p.Ser9Phe (c.26C>T) pathogenic?

MAP3K7 p.Ser9Phe (c.26C>T) is classified Conflicting classifications of pathogenicity in MAP3K7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.1407); Ultra-rare (popmax 0.0377%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP3K7 p.Ser9Phe (c.26C>T)?

MAP3K7 p.Ser9Phe (c.26C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K7 p.Ser9Phe (c.26C>T) in the general population?

MAP3K7 p.Ser9Phe (c.26C>T) is ultra-rare (popmax 0.0377%, nfe) (gnomAD).

What do computational predictors say about MAP3K7 p.Ser9Phe (c.26C>T)?

AlphaMissense predicts likely benign (score 0.1407) — an in-silico prediction, not a clinical call.

MAP3K7 p.Ser9Phe

c.26C>T · rs139666795 · VCV1014964

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1407 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0377%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1407	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
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 0.99	unconstrained · MANE · 102 bp · p 0.95 · regional, not allelic
Overall
CADD	23.7	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 0.0377% European (non-Finnish) · 444/1,178,758 alleles

Filtering AF 0.0347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.0284% 458/1,611,302 alleles · ultra-rare exomes 438/1,459,040 · genomes 20/152,262 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0377%	2,655
Remaining individualsnot grpmax-eligible	0.0177%	5,664
African / African-American	0.00268%	37,299
East Asian	0.00225%	44,446

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: MAP3K7
Protein: p.Ser9Phe
Coding: c.26C>T
MANE Select: NM_145331
dbSNP: rs139666795
Type: single nucleotide variant
Location: chr6:90586858 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 9: the 'interaction with mapk8ip1' region

Full MAP3K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Arg289Gln Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Arg347His Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Asn342Asp Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Gly411Asp Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Gly451Ser Uncertain significance ★★ ⚠ same condition

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/map3k7-p-ser9phe (accessed [today's date]).

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