Is MAP4K3 p.Arg602Gln (c.1805G>A) pathogenic?

MAP4K3 p.Arg602Gln (c.1805G>A) is classified Uncertain significance in MAP4K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely pathogenic (0.6884); Ultra-rare (popmax 0.0112%, eas).

How common is MAP4K3 p.Arg602Gln (c.1805G>A) in the general population?

MAP4K3 p.Arg602Gln (c.1805G>A) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about MAP4K3 p.Arg602Gln (c.1805G>A)?

AlphaMissense predicts likely pathogenic (score 0.6884) — an in-silico prediction, not a clinical call.

MAP4K3 p.Arg602Gln

c.1805G>A · VCV3542987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6884 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6884	likely pathogenic
REVEL	0.304	indeterminate
SaProt	LLR -13.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Pangolin	Δ0.35	loss · gain 0.02 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 76 kb · p 0.027 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0112% East Asian · 5/44,764 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00174% 28/1,612,796 alleles · ultra-rare exomes 24/1,460,862 · genomes 4/151,934 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,953
Admixed American	0.005%	19,988
African / African-American	0.00267%	37,411
European (non-Finnish)	0.00144%	69,374
South Asian	0.0011%	90,976

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.Arg602Gln
Coding: c.1805G>A
MANE Select: NM_003618
Type: single nucleotide variant
Location: chr2:39272532 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.96 · 1 PDB
Residue 602: the cnh domain

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-arg602gln (accessed [today's date]).

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