Is MAP7 p.Trp330Arg (c.988T>C) pathogenic?

MAP7 p.Trp330Arg (c.988T>C) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.4707); Very rare (popmax 0.00669%, eas).

How common is MAP7 p.Trp330Arg (c.988T>C) in the general population?

MAP7 p.Trp330Arg (c.988T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about MAP7 p.Trp330Arg (c.988T>C)?

AlphaMissense predicts ambiguous (score 0.4707) — an in-silico prediction, not a clinical call.

MAP7 p.Trp330Arg

c.988T>C · VCV4549650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4707	ambiguous
REVEL	0.068	moderately benign-leaning
SaProt	LLR -2.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 4.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	16.79	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 0.00669% East Asian · 3/44,876 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,613,370 alleles · very rare exomes 6/1,461,074 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,959
South Asian	0.0022%	45,529
Admixed American	0.00167%	60,022

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.Trp330Arg
Coding: c.988T>C
MANE Select: NM_003980
Type: single nucleotide variant
Location: chr6:136366328 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB
Residue 330: 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-trp330arg (accessed [today's date]).

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