Is MAP4 p.Val549= (c.1647C>T) pathogenic?

MAP4 p.Val549= (c.1647C>T) is classified Likely benign in MAP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-09). Rare (popmax 0.193%, afr); Associated with MAP4-related disorder.

What condition is associated with MAP4 p.Val549= (c.1647C>T)?

MAP4 p.Val549= (c.1647C>T) is associated with MAP4-related disorder (ClinVar).

How common is MAP4 p.Val549= (c.1647C>T) in the general population?

MAP4 p.Val549= (c.1647C>T) is rare (popmax 0.193%, afr) (gnomAD).

MAP4 p.Val549=

c.1647C>T · rs146972984 · VCV3035749

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.193%, afr)

Conditions

MAP4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP -2.9
Overall
CADD	0.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.193% African / African-American · 145/75,032 alleles

Filtering AF 0.168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.00979% 158/1,614,156 alleles · rare exomes 78/1,461,890 · genomes 80/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.193%	517
Admixed American	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0096%	10,418

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.Val549=
Coding: c.1647C>T
MANE Select: NM_001385682
dbSNP: rs146972984
Type: single nucleotide variant
Location: chr3:47916180 (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

Disease context

MAP4-related disorder

Similar variants

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
MAP4 p.Arg23Gln Benign same condition
MAP4 p.Arg23Trp 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-val549 (accessed [today's date]).

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