Is MAP4 p.Val37Asp (c.110T>A) pathogenic?

MAP4 p.Val37Asp (c.110T>A) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.687); Ultra-rare (popmax 0.0165%, mid).

How common is MAP4 p.Val37Asp (c.110T>A) in the general population?

MAP4 p.Val37Asp (c.110T>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about MAP4 p.Val37Asp (c.110T>A)?

AlphaMissense predicts likely pathogenic (score 0.687) — an in-silico prediction, not a clinical call.

MAP4 p.Val37Asp

c.110T>A · VCV4103473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.687	likely pathogenic
REVEL	0.268	benign-leaning
SaProt	LLR -4.01	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	23.2	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00403% 65/1,613,970 alleles · ultra-rare exomes 54/1,461,734 · genomes 11/152,236 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.00466%	21,452
East Asian	0.00223%	44,876
South Asian	0.0022%	45,536
Admixed American	0.00167%	60,024
African / African-American	0.00133%	75,008

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.Val37Asp
Coding: c.110T>A
MANE Select: NM_001385682
Type: single nucleotide variant
Location: chr3:47998751 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03

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

Similar variants

MAP4 p.Val37= Benign ★★ same residue
MAP4 c.292+9T>G Benign ★★ same type
MAP4 p.Gln1950= Benign ★★ same type
MAP4 p.Leu516= Likely 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-val37asp (accessed [today's date]).

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