Is MAP1A p.Ala2165Val (c.6494C>T) pathogenic?

MAP1A p.Ala2165Val (c.6494C>T) is classified Uncertain significance in MAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: ambiguous (0.3541); Very rare (popmax 0.00568%, nfe).

How common is MAP1A p.Ala2165Val (c.6494C>T) in the general population?

MAP1A p.Ala2165Val (c.6494C>T) is very rare (popmax 0.00568%, nfe) (gnomAD).

What do computational predictors say about MAP1A p.Ala2165Val (c.6494C>T)?

AlphaMissense predicts ambiguous (score 0.3541) — an in-silico prediction, not a clinical call.

MAP1A p.Ala2165Val

c.6494C>T · VCV3542571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3541	ambiguous
REVEL	0.086	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00568% European (non-Finnish) · 67/1,180,038 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00421% 68/1,614,014 alleles · very rare exomes 63/1,461,812 · genomes 5/152,202 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,613
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: MAP1A
Protein: p.Ala2165Val
Coding: c.6494C>T
MANE Select: NM_002373
Type: single nucleotide variant
Location: chr15:43527967 (GRCh38)
Structure: AlphaFold pLDDT 94.44 · 41 PDB

Full MAP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP1A p.Arg2734Gln Uncertain significance ★★ same type
MAP1A p.Gly567Ala Uncertain significance ★★ ⚠ same type
MAP1A p.Gly482= Benign/Likely benign ★★ same type
MAP1A p.Leu1621Val Benign ★★ same type
MAP1A p.Ser1152= Likely benign ★★ same type
MAP1A p.Ser1311= Benign/Likely benign ★★ same type
MAP1A p.Ser1544= Benign ★★ same type
MAP1A p.Ser1858Cys Likely benign ★★ 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/map1a-p-ala2165val (accessed [today's date]).

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