Is MAP4 p.Glu2239Lys (c.6715G>A) pathogenic?

MAP4 p.Glu2239Lys (c.6715G>A) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1752); Ultra-rare (popmax 0.0395%, mid).

How common is MAP4 p.Glu2239Lys (c.6715G>A) in the general population?

MAP4 p.Glu2239Lys (c.6715G>A) is ultra-rare (popmax 0.0395%, mid) (gnomAD).

What do computational predictors say about MAP4 p.Glu2239Lys (c.6715G>A)?

AlphaMissense predicts likely benign (score 0.1752) — an in-silico prediction, not a clinical call.

MAP4 p.Glu2239Lys

c.6715G>A · rs767474005 · VCV3123061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1752	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.92	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 5.9	GERP 0.72, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 23 kb · p 0.28 · regional, not allelic
Overall
CADD	26.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E1094K vs ClinVar E2239K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% Middle Eastern · 2/5,064 alleles

Filtering AF 0.0264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.00261% 42/1,607,798 alleles · ultra-rare exomes 36/1,455,664 · genomes 6/152,134 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0395%	2,532
Admixed American	0.0388%	2,579
African / African-American	0.00802%	12,471
South Asian	0.0022%	45,397
Remaining individualsnot grpmax-eligible	0.00161%	62,188
European (non-Finnish)	0.000679%	147,325

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: MAP4
Protein: p.Glu2239Lys
Coding: c.6715G>A
MANE Select: NM_001385682
dbSNP: rs767474005
Type: single nucleotide variant
Location: chr3:47853334 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 1094 UniProt numbering: the 'disordered' region

Full MAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4 c.292+9T>G Benign ★★ same type
MAP4 p.Gln1950= Benign ★★ same type
MAP4 p.Leu516= Likely benign ★★ same type
MAP4 p.Val37= Benign ★★ same type
MAP4 p.Ala150Ser Uncertain significance ★ ⚠ same type
MAP4 p.Ala1922Val Uncertain significance ★ ⚠ same type
MAP4 p.Ala1926Pro Uncertain significance ★ ⚠ same type
MAP4 p.Ala1941Thr 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/map4-p-glu2239lys (accessed [today's date]).

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