Is MAP1A p.His165Pro (c.494A>C) pathogenic?

MAP1A p.His165Pro (c.494A>C) is classified Uncertain significance in MAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-09). AlphaMissense: likely pathogenic (0.9856); Ultra-rare (popmax 0.027%, nfe).

How common is MAP1A p.His165Pro (c.494A>C) in the general population?

MAP1A p.His165Pro (c.494A>C) is ultra-rare (popmax 0.027%, nfe) (gnomAD).

What do computational predictors say about MAP1A p.His165Pro (c.494A>C)?

AlphaMissense predicts likely pathogenic (score 0.9856) — an in-silico prediction, not a clinical call.

MAP1A p.His165Pro

c.494A>C · rs2079320981 · VCV2278716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, nfe)

Computational evidence

Protein change
AlphaMissense	0.9856	likely pathogenic
REVEL	0.553	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Overall
CADD	26.8	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 0.027% European (non-Finnish) · 317/1,175,686 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.0217% 350/1,609,394 alleles · ultra-rare exomes 349/1,457,106 · genomes 1/152,288 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.027%	3,709
Remaining individualsnot grpmax-eligible	0.0225%	4,454
Middle Eastern	0.0165%	6,048
African / African-American	0.0107%	9,370
South Asian	0.00879%	11,373
East Asian	0.00446%	22,426

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.His165Pro
Coding: c.494A>C
MANE Select: NM_002373
dbSNP: rs2079320981
Type: single nucleotide variant
Location: chr15:43521967 (GRCh38)
Structure: AlphaFold pLDDT 94.44 · 41 PDB
Residue 165: an α-helix

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-his165pro (accessed [today's date]).

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