Is MAP3K13 p.Phe120Ile (c.358T>A) pathogenic?

MAP3K13 p.Phe120Ile (c.358T>A) is classified Uncertain significance in MAP3K13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: ambiguous (0.4506); Very rare (popmax 0.00534%, nfe).

How common is MAP3K13 p.Phe120Ile (c.358T>A) in the general population?

MAP3K13 p.Phe120Ile (c.358T>A) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about MAP3K13 p.Phe120Ile (c.358T>A)?

AlphaMissense predicts ambiguous (score 0.4506) — an in-silico prediction, not a clinical call.

MAP3K13 p.Phe120Ile

c.358T>A · rs200728282 · VCV3122874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4506 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4506	ambiguous
REVEL	0.313	indeterminate
SaProt	LLR -5.34	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.82 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 381 bp · p 0.77 · regional, not allelic
Overall
CADD	24.7	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 0.00534% European (non-Finnish) · 63/1,180,038 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00434% 70/1,614,014 alleles · very rare exomes 62/1,461,882 · genomes 8/152,132 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00534%	18,731
African / African-American	0.00401%	24,968
South Asian	0.0022%	45,543
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: MAP3K13
Protein: p.Phe120Ile
Coding: c.358T>A
MANE Select: NM_004721
dbSNP: rs200728282
Type: single nucleotide variant
Location: chr3:185428939 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.92

Full MAP3K13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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MAP3K13 p.Arg278His Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg326Trp Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg401Gln Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg449Gln Uncertain significance ★ same type
MAP3K13 p.Arg474Gln 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/map3k13-p-phe120ile (accessed [today's date]).

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