Is MAP4 p.Arg1900His (c.5699G>A) pathogenic?

MAP4 p.Arg1900His (c.5699G>A) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: ambiguous (0.3974); Very rare (popmax 0.00549%, sas).

How common is MAP4 p.Arg1900His (c.5699G>A) in the general population?

MAP4 p.Arg1900His (c.5699G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about MAP4 p.Arg1900His (c.5699G>A)?

AlphaMissense predicts ambiguous (score 0.3974) — an in-silico prediction, not a clinical call.

MAP4 p.Arg1900His

c.5699G>A · VCV3542953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3974	ambiguous
REVEL	0.237	benign-leaning
SaProt	LLR -8.69	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 23 kb · p 0.28 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R755H vs ClinVar R1900H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,062 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00167% 27/1,613,832 alleles · very rare exomes 27/1,461,618 · genomes 0/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,212
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.00161%	62,105

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.Arg1900His
Coding: c.5699G>A
MANE Select: NM_001385682
Type: single nucleotide variant
Location: chr3:47875743 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 755 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-arg1900his (accessed [today's date]).

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