Is MAP1B p.Ala2275Val (c.6824C>T) pathogenic?

MAP1B p.Ala2275Val (c.6824C>T) is classified Conflicting classifications of pathogenicity in MAP1B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Ala2275Val (c.6824C>T)?

MAP1B p.Ala2275Val (c.6824C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Ala2275Val (c.6824C>T) in the general population?

MAP1B p.Ala2275Val (c.6824C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about MAP1B p.Ala2275Val (c.6824C>T)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

MAP1B p.Ala2275Val

c.6824C>T · rs150487096 · VCV2211325

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.15	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 0.47	GERP -5.1, phastCons 0.025
Regional constraint	o/e 0.71	unconstrained · MANE · 5,431 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	5.466	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00155% 25/1,614,082 alleles · ultra-rare exomes 22/1,461,884 · genomes 3/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00549%	18,219
Remaining individualsnot grpmax-eligible	0.0032%	31,245
East Asian	0.00223%	44,898
African / African-American	0.00133%	74,916
European (non-Finnish)	0.00127%	78,669

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.Ala2275Val
Coding: c.6824C>T
MANE Select: NM_005909
dbSNP: rs150487096
Type: single nucleotide variant
Location: chr5:72200179 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 2275: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1480Tyr Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1993Gly Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu2435Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly919Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly932Ser Uncertain significance ★★ ⚠ same condition
MAP1B p.Lys1025Arg Uncertain significance ★★ ⚠ 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/map1b-p-ala2275val (accessed [today's date]).

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