Is MAP4 p.Ile386Val (c.1156A>G) pathogenic?

MAP4 p.Ile386Val (c.1156A>G) is classified Benign in MAP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-12). AlphaMissense: likely benign (0.0872); Rare (popmax 0.115%, mid); Associated with MAP4-related disorder.

What condition is associated with MAP4 p.Ile386Val (c.1156A>G)?

MAP4 p.Ile386Val (c.1156A>G) is associated with MAP4-related disorder (ClinVar).

How common is MAP4 p.Ile386Val (c.1156A>G) in the general population?

MAP4 p.Ile386Val (c.1156A>G) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about MAP4 p.Ile386Val (c.1156A>G)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

MAP4 p.Ile386Val

c.1156A>G · rs142423472 · VCV3035104

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAP4-related disorder

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -9.86	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 -1.8	GERP -1.6
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	0.191	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 0.115% Middle Eastern · 7/6,084 alleles

Filtering AF 0.054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.0527% 850/1,614,072 alleles · rare exomes 771/1,461,846 · genomes 79/152,226 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.7%	59
Remaining individualsnot grpmax-eligible	0.155%	644
Middle Easterngrpmax	0.115%	869
European (non-Finnish)	0.0192%	5,221
South Asian	0.0121%	8,279
Admixed American	0.00833%	12,002
African / African-American	0.00267%	37,473

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile386Val
Coding: c.1156A>G
MANE Select: NM_001385682
dbSNP: rs142423472
Type: single nucleotide variant
Location: chr3:47916671 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 386: the '17 x 14 aa tandem repeats' region; the 'disordered' region

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

Disease context

MAP4-related disorder

Similar variants

MAP4 p.Ile386Thr Uncertain significance ★ ⚠ 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.Arg23Gln 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-ile386val (accessed [today's date]).

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