Is MAP4 p.Arg23Trp (c.67C>T) pathogenic?

MAP4 p.Arg23Trp (c.67C>T) is classified Likely benign in MAP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-24). AlphaMissense: likely pathogenic (0.829); Rare (popmax 0.38%, amr); Associated with MAP4-related disorder.

What condition is associated with MAP4 p.Arg23Trp (c.67C>T)?

MAP4 p.Arg23Trp (c.67C>T) is associated with MAP4-related disorder (ClinVar).

How common is MAP4 p.Arg23Trp (c.67C>T) in the general population?

MAP4 p.Arg23Trp (c.67C>T) is rare (popmax 0.38%, amr) (gnomAD).

What do computational predictors say about MAP4 p.Arg23Trp (c.67C>T)?

AlphaMissense predicts likely pathogenic (score 0.829) — an in-silico prediction, not a clinical call.

MAP4 p.Arg23Trp

c.67C>T · rs760742452 · VCV3034536

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.829 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.38%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MAP4-related disorder

Computational evidence

Protein change
AlphaMissense	0.829	likely pathogenic · top 8% in MAP4
REVEL	0.357	indeterminate
SaProt	LLR -9.73	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	24.8	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 0.38% Admixed American · 228/59,986 alleles

Filtering AF 0.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.324%

Overall 0.0182% 294/1,613,962 alleles · rare exomes 275/1,461,848 · genomes 19/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.38%	263
Remaining individualsnot grpmax-eligible	0.0144%	6,943
Finnishnot grpmax-eligible	0.00469%	21,344
South Asian	0.00439%	22,769
European (non-Finnish)	0.00415%	24,082
African / African-American	0.00134%	74,884

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.Arg23Trp
Coding: c.67C>T
MANE Select: NM_001385682
dbSNP: rs760742452
Type: single nucleotide variant
Location: chr3:47998794 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 23: a UniProt-annotated variant site (in)

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

Disease context

MAP4-related disorder

Similar variants

MAP4 p.Arg23Gln Benign same residue
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.Asn569= 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-arg23trp (accessed [today's date]).

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