Is MAP7 p.Thr474Ala (c.1420A>G) pathogenic?

MAP7 p.Thr474Ala (c.1420A>G) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: ambiguous (0.5372); Very rare (popmax 6.2e-05%).

How common is MAP7 p.Thr474Ala (c.1420A>G) in the general population?

MAP7 p.Thr474Ala (c.1420A>G) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about MAP7 p.Thr474Ala (c.1420A>G)?

AlphaMissense predicts ambiguous (score 0.5372) — an in-silico prediction, not a clinical call.

MAP7 p.Thr474Ala

c.1420A>G · VCV4103622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5372 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
AlphaMissense	0.5372	ambiguous
REVEL	0.402	indeterminate
SaProt	LLR -9.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	24.5	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 6.2e-05%

Overall 6.2e-05% 1/1,614,142 alleles · very rare exomes 1/1,461,892 · genomes 0/152,250 · joint denominator

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: MAP7
Protein: p.Thr474Ala
Coding: c.1420A>G
MANE Select: NM_003980
Type: single nucleotide variant
Location: chr6:136362556 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB
Residue 474: the 'disordered' region

Full MAP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP7 p.Arg214Cys Uncertain significance ★★ ⚠ same type
MAP7 c.1274-1G>C Uncertain significance ★ same type
MAP7 c.67+24403G>A Uncertain significance ★ same type
MAP7 c.67+24406A>G Uncertain significance ★ same type
MAP7 c.67+24434G>T Uncertain significance ★ same type
MAP7 c.752-21T>C Uncertain significance ★ same type
MAP7 c.752-6G>A Uncertain significance ★ same type
MAP7 p.Ala17Val 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/map7-p-thr474ala (accessed [today's date]).

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