Is MAP4K3 p.Val489Ile (c.1465G>A) pathogenic?

MAP4K3 p.Val489Ile (c.1465G>A) is classified Likely benign in MAP4K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0681); Very rare (popmax 0.00167%, amr).

How common is MAP4K3 p.Val489Ile (c.1465G>A) in the general population?

MAP4K3 p.Val489Ile (c.1465G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MAP4K3 p.Val489Ile (c.1465G>A)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

MAP4K3 p.Val489Ile

c.1465G>A · rs1200447390 · VCV2382801

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -7.31	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 -5.5	GERP -3.5
Regional constraint	o/e 1.08	unconstrained · MANE · 76 kb · p 0.027 · regional, not allelic
Overall
CADD	0.323	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 0.00167% Admixed American · 1/59,982 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,613,788 alleles · very rare exomes 6/1,461,720 · genomes 2/152,068 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,982
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000509%	196,656

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.Val489Ile
Coding: c.1465G>A
MANE Select: NM_003618
dbSNP: rs1200447390
Type: single nucleotide variant
Location: chr2:39288130 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.96 · 1 PDB
Residue 489: 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-val489ile (accessed [today's date]).

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