Is MAP4K3 p.Asp414Glu (c.1242T>A) pathogenic?

MAP4K3 p.Asp414Glu (c.1242T>A) is classified Uncertain significance in MAP4K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.1238); Ultra-rare (popmax 0.0307%, afr).

How common is MAP4K3 p.Asp414Glu (c.1242T>A) in the general population?

MAP4K3 p.Asp414Glu (c.1242T>A) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about MAP4K3 p.Asp414Glu (c.1242T>A)?

AlphaMissense predicts likely benign (score 0.1238) — an in-silico prediction, not a clinical call.

MAP4K3 p.Asp414Glu

c.1242T>A · VCV4051448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1238 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1238	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -5.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 76 kb · p 0.027 · regional, not allelic
Overall
CADD	18.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,910 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00149% 24/1,613,270 alleles · ultra-rare exomes 7/1,461,108 · genomes 17/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,257
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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: MAP4K3
Protein: p.Asp414Glu
Coding: c.1242T>A
MANE Select: NM_003618
Type: single nucleotide variant
Location: chr2:39292802 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.96 · 1 PDB
Residue 414: the 'disordered' region

Full MAP4K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4K3 p.Ala253Thr Uncertain significance ★ ⚠ same type
MAP4K3 p.Ala310Val Uncertain significance ★ ⚠ same type
MAP4K3 p.Ala391Glu Uncertain significance ★ ⚠ same type
MAP4K3 p.Ala429Val Uncertain significance ★ ⚠ same type
MAP4K3 p.Ala621Thr Uncertain significance ★ ⚠ same type
MAP4K3 p.Ala664Pro Uncertain significance ★ ⚠ same type
MAP4K3 p.Ala75Thr Uncertain significance ★ ⚠ same type
MAP4K3 p.Arg482Lys 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/map4k3-p-asp414glu (accessed [today's date]).

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