Is MAP4K5 p.Ala328Val (c.983C>T) pathogenic?

MAP4K5 p.Ala328Val (c.983C>T) is classified Uncertain significance in MAP4K5 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0697); Very rare (popmax 0.00364%, amr).

How common is MAP4K5 p.Ala328Val (c.983C>T) in the general population?

MAP4K5 p.Ala328Val (c.983C>T) is very rare (popmax 0.00364%, amr) (gnomAD).

What do computational predictors say about MAP4K5 p.Ala328Val (c.983C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

MAP4K5 p.Ala328Val

c.983C>T · VCV4103577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.12	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	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 49 kb · p 0.0017 · regional, not allelic
Overall
CADD	19.33	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 0.00364% Admixed American · 2/54,946 alleles

Filtering AF 0.000604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000226%

Overall 0.000443% 7/1,580,084 alleles · very rare exomes 5/1,428,064 · genomes 2/152,020 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00364%	27,473
European (non-Finnish)	0.00043%	232,348

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: MAP4K5
Protein: p.Ala328Val
Coding: c.983C>T
MANE Select: NM_006575
Type: single nucleotide variant
Location: chr14:50456548 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.15
Residue 328: the 'disordered' region

Full MAP4K5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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MAP4K5 p.Val731= Benign ★★ same type
MAP4K5 c.1709-2A>T Uncertain significance ★ same type
MAP4K5 p.Ala278Thr Uncertain significance ★ ⚠ same type
MAP4K5 p.Ala37Val Uncertain significance ★ ⚠ same type
MAP4K5 p.Ala425Thr Uncertain significance ★ ⚠ same type
MAP4K5 p.Ala464Thr 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/map4k5-p-ala328val (accessed [today's date]).

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