Is MAP4 p.Val133= (c.399C>T) pathogenic?

MAP4 p.Val133= (c.399C>T) is classified Benign in MAP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-08). Common (popmax 30.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MAP4-related disorder.

What condition is associated with MAP4 p.Val133= (c.399C>T)?

MAP4 p.Val133= (c.399C>T) is associated with MAP4-related disorder (ClinVar).

MAP4 p.Val133=

Q: How common is MAP4 p.Val133= (c.399C>T) in the general population?

MAP4 p.Val133= (c.399C>T) is common (popmax 30.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.399C>T · rs20565 · VCV3055841

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 30.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

MAP4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.007	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.44	GERP -2.6, phastCons 0.13
Overall
CADD	8.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.2% African / African-American · 22,659/74,928 alleles

Filtering AF 29.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.8%

Overall 1.67% 26,959/1,613,986 alleles · common exomes 13,651/1,461,802 · genomes 13,308/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.2%	3
Admixed American	2.48%	40
Remaining individualsnot grpmax-eligible	2.2%	46
Middle Eastern	1.47%	68
Ashkenazi Jewishnot grpmax-eligible	0.493%	203
European (non-Finnish)	0.0991%	1,009
South Asian	0.0362%	2,759
Finnishnot grpmax-eligible	0.00156%	64,028

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.Val133=
Coding: c.399C>T
MANE Select: NM_001385682
dbSNP: rs20565
Type: single nucleotide variant
Location: chr3:47928244 (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-val133 (accessed [today's date]).

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