Is MAP4 p.Asp491Asn (c.1471G>A) pathogenic?

MAP4 p.Asp491Asn (c.1471G>A) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.0926); Rare (popmax 0.105%, sas).

How common is MAP4 p.Asp491Asn (c.1471G>A) in the general population?

MAP4 p.Asp491Asn (c.1471G>A) is rare (popmax 0.105%, sas) (gnomAD).

What do computational predictors say about MAP4 p.Asp491Asn (c.1471G>A)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

MAP4 p.Asp491Asn

c.1471G>A · VCV3870280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.36	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 0.5	GERP -1.4, phastCons 0.002
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	11.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% South Asian · 96/91,088 alleles

Filtering AF 0.0883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0819%

Overall 0.0062% 100/1,614,134 alleles · rare exomes 98/1,461,892 · genomes 2/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.105%	949
Remaining individualsnot grpmax-eligible	0.0064%	15,623

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.Asp491Asn
Coding: c.1471G>A
MANE Select: NM_001385682
Type: single nucleotide variant
Location: chr3:47916356 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 491: the '17 x 14 aa tandem repeats' region

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

Similar variants

MAP4 p.Asp491Val Uncertain significance ★ ⚠ 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.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

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-asp491asn (accessed [today's date]).

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