Is MAP4K2 p.Ala806Val (c.2417C>T) pathogenic?

MAP4K2 p.Ala806Val (c.2417C>T) is classified Uncertain significance in MAP4K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: ambiguous (0.3427); Very rare (popmax 0.00224%, eas).

How common is MAP4K2 p.Ala806Val (c.2417C>T) in the general population?

MAP4K2 p.Ala806Val (c.2417C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about MAP4K2 p.Ala806Val (c.2417C>T)?

AlphaMissense predicts ambiguous (score 0.3427) — an in-silico prediction, not a clinical call.

MAP4K2 p.Ala806Val

c.2417C>T · VCV4549568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3427 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Computational evidence

Protein change
AlphaMissense	0.3427	ambiguous
REVEL	0.379	indeterminate
SaProt	LLR -9.25	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 897 bp · p 5e-06 · regional, not allelic
Overall
CADD	27.0	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 0.00224% East Asian · 1/44,628 alleles

Filtering AF 0.000372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000623% 10/1,604,570 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,628
South Asian	0.00224%	44,640
European (non-Finnish)	0.000595%	167,939

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.Ala806Val
Coding: c.2417C>T
MANE Select: NM_004579
Type: single nucleotide variant
Location: chr11:64789583 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.32

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

Similar variants

MAP4K2 p.Ala806= Benign ★ 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-ala806val (accessed [today's date]).

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