Is MAP4K5 p.Val731= (c.2193A>G) pathogenic?

MAP4K5 p.Val731= (c.2193A>G) is classified Benign in MAP4K5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-08-03). Common (popmax 5.25%, afr) — too common for a highly-penetrant pathogenic allele.

MAP4K5 p.Val731=

Q: How common is MAP4K5 p.Val731= (c.2193A>G) in the general population?

MAP4K5 p.Val731= (c.2193A>G) is common (popmax 5.25%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2193A>G · rs34382193 · VCV783688

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.25%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -1.9, phastCons 0.98
Overall
CADD	9.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.25% African / African-American · 3,866/73,630 alleles

Filtering AF 5.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.06%

Overall 0.286% 4,473/1,564,206 alleles · common exomes 2,119/1,411,902 · genomes 2,354/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.25%	19
Admixed American	0.436%	229
Remaining individualsnot grpmax-eligible	0.381%	263
Middle Eastern	0.217%	461
South Asian	0.0142%	7,057
European (non-Finnish)	0.0103%	9,687

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.Val731=
Coding: c.2193A>G
MANE Select: NM_006575
dbSNP: rs34382193
Type: single nucleotide variant
Location: chr14:50429232 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.15
Residue 731: the cnh domain

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

Similar variants

MAP4K5 p.Val739Ile Uncertain significance ★★ ⚠ same type
ATL1 c.-140+55A>T Benign ★★ same type
MAP4K5 c.1709-2A>T Uncertain significance ★ same type
MAP4K5 p.Ala278Thr Uncertain significance ★ ⚠ same type
MAP4K5 p.Ala328Val 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-val731 (accessed [today's date]).

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