Is MAP4K4 p.Val481Ile (c.1441G>A) pathogenic?

MAP4K4 p.Val481Ile (c.1441G>A) is classified Likely benign in MAP4K4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.0548); Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with MAP4K4 p.Val481Ile (c.1441G>A)?

MAP4K4 p.Val481Ile (c.1441G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAP4K4 p.Val481Ile (c.1441G>A) in the general population?

MAP4K4 p.Val481Ile (c.1441G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about MAP4K4 p.Val481Ile (c.1441G>A)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

MAP4K4 p.Val481Ile

c.1441G>A · rs780708201 · VCV2600682

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -4.62	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 1.5	GERP -2.4, phastCons 0.94
Regional constraint	o/e 0.81	unconstrained · MANE · 18 kb · p 1e-07 · regional, not allelic
Overall
CADD	10.62	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 0.0134% East Asian · 6/44,850 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,612,136 alleles · ultra-rare exomes 5/1,459,966 · genomes 1/152,170 · joint denominator

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: MAP4K4
Protein: p.Val481Ile
Coding: c.1441G>A
MANE Select: NM_001395002
dbSNP: rs780708201
Type: single nucleotide variant
Location: chr2:101859041 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.47 · 19 PDB

Full MAP4K4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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MAP4K4 p.Leu742Pro Uncertain significance ★★ ⚠ same condition
MAP4K4 p.Ser758Phe Uncertain significance ★★ ⚠ same condition
MAP4K4 p.Asp203Gly Likely pathogenic ★ same condition
MAP4K4 p.Gln402Ter Pathogenic ★ same condition
MAP4K4 p.Gly173Asp Pathogenic ★ same condition
MAP4K4 p.Lys54Arg Likely pathogenic ★ same condition

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/map4k4-p-val481ile (accessed [today's date]).

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