Is MAP1B p.Ile594Val (c.1780A>G) pathogenic?

MAP1B p.Ile594Val (c.1780A>G) is classified Benign in MAP1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.06); Common (popmax 97.1%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about MAP1B p.Ile594Val (c.1780A>G)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

MAP1B p.Ile594Val

Q: How common is MAP1B p.Ile594Val (c.1780A>G) in the general population?

MAP1B p.Ile594Val (c.1780A>G) is common (popmax 97.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1780A>G · rs1866374 · VCV1271364

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 97.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.06	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -4.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.32	GERP -4.8
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	0.399	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 97.1% East Asian · 43,518/44,816 alleles

Filtering AF 96.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 96%

Overall 83.5% 1,347,300/1,613,620 alleles · common exomes 1,216,587/1,461,638 · genomes 130,713/151,982 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	97.1%	1
African / African-American	96.9%	1
South Asian	90%	1
Middle Eastern	84.5%	1
Remaining individualsnot grpmax-eligible	84%	1
European (non-Finnish)	82.6%	1
Amishnot grpmax-eligible	82%	1
Ashkenazi Jewishnot grpmax-eligible	81%	1
Finnishnot grpmax-eligible	80.2%	1
Admixed American	69%	1

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: MAP1B
Protein: p.Ile594Val
Coding: c.1780A>G
MANE Select: NM_005909
dbSNP: rs1866374
Type: single nucleotide variant
Location: chr5:72195135 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 594: the 'disordered' region; a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in)

Full MAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP1B p.Arg1664Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg2140Ter Pathogenic ★★ same type
MAP1B p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg85Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same type
MAP1B p.Arg1399Cys Uncertain significance ★★ ⚠ same type
MAP1B p.Arg1948Trp 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/map1b-p-ile594val (accessed [today's date]).

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