Is MAP4K2 p.Lys403Asn (c.1209G>T) pathogenic?

MAP4K2 p.Lys403Asn (c.1209G>T) is classified Uncertain significance in MAP4K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-05). AlphaMissense: likely pathogenic (0.9276); Ultra-rare (popmax 0.0214%, afr).

How common is MAP4K2 p.Lys403Asn (c.1209G>T) in the general population?

MAP4K2 p.Lys403Asn (c.1209G>T) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about MAP4K2 p.Lys403Asn (c.1209G>T)?

AlphaMissense predicts likely pathogenic (score 0.9276) — an in-silico prediction, not a clinical call.

MAP4K2 p.Lys403Asn

c.1209G>T · rs145384465 · VCV2258838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9276 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9276	likely pathogenic
REVEL	0.034	moderately benign-leaning
SaProt	LLR -9.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -1.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 13 kb · p 0.0094 · regional, not allelic
Overall
CADD	22.7	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 0.0214% African / African-American · 16/74,794 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.001% 16/1,598,700 alleles · ultra-rare

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: MAP4K2
Protein: p.Lys403Asn
Coding: c.1209G>T
MANE Select: NM_004579
dbSNP: rs145384465
Type: single nucleotide variant
Location: chr11:64797342 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.32
Residue 403: the 'disordered' region

Full MAP4K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4K2 p.Lys403Thr Uncertain significance ★ ⚠ same residue
MAP4K2 p.Ala120Ser Benign ★★ same type
MAP4K2 p.Asn606= Benign ★★ same type
MAP4K2 p.Ala183Asp Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala184Ser Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala405Thr Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala487Thr Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala790Asp 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/map4k2-p-lys403asn (accessed [today's date]).

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