Is MAP4 p.Val628Ile (c.1882G>A) pathogenic?

MAP4 p.Val628Ile (c.1882G>A) is classified Benign in MAP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-25). AlphaMissense: likely benign (0.0793); Common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MAP4-related disorder.

What condition is associated with MAP4 p.Val628Ile (c.1882G>A)?

MAP4 p.Val628Ile (c.1882G>A) is associated with MAP4-related disorder (ClinVar).

What do computational predictors say about MAP4 p.Val628Ile (c.1882G>A)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

MAP4 p.Val628Ile

Q: How common is MAP4 p.Val628Ile (c.1882G>A) in the general population?

MAP4 p.Val628Ile (c.1882G>A) is common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1882G>A · rs1137524 · VCV3060070

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAP4-related disorder

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1	GERP -2.9
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	1.752	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 52.5% African / African-American · 39,286/74,842 alleles

Filtering AF 52.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.9%

Overall 32% 515,628/1,613,292 alleles · common exomes 460,073/1,461,510 · genomes 55,555/151,782 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	52.5%	2
Middle Eastern	38.2%	3
Admixed American	37.6%	3
Ashkenazi Jewishnot grpmax-eligible	37.4%	3
South Asian	37.2%	3
Remaining individualsnot grpmax-eligible	33.6%	3
European (non-Finnish)	30.5%	3
Amishnot grpmax-eligible	29.6%	3
East Asian	27%	4
Finnishnot grpmax-eligible	21.7%	5

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.Val628Ile
Coding: c.1882G>A
MANE Select: NM_001385682
dbSNP: rs1137524
Type: single nucleotide variant
Location: chr3:47914934 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 628: a UniProt-annotated variant site (in)

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

Disease context

MAP4-related disorder

Similar variants

MAP4 p.Val628= Likely benign same residue
MAP4 p.Val628Ala Uncertain significance ★ ⚠ same residue
MAP4 c.292+2409G>A Likely benign same condition
MAP4 c.*100G>A Likely benign same condition
MAP4 c.*44G>A Likely benign same condition
MAP4 p.Ala2123= Likely benign same condition
MAP4 p.Ala2134= Likely benign same condition
MAP4 p.Ala437= Likely benign 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/map4-p-val628ile (accessed [today's date]).

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