Is MAP7 p.Arg415Trp (c.1243C>T) pathogenic?

MAP7 p.Arg415Trp (c.1243C>T) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely benign (0.1184); Ultra-rare (popmax 0.0253%, sas).

How common is MAP7 p.Arg415Trp (c.1243C>T) in the general population?

MAP7 p.Arg415Trp (c.1243C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about MAP7 p.Arg415Trp (c.1243C>T)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

MAP7 p.Arg415Trp

c.1243C>T · VCV3870365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 3.9, phastCons 0.028
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	18.39	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 0.0253% South Asian · 23/91,082 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00242% 39/1,613,884 alleles · ultra-rare exomes 34/1,461,784 · genomes 5/152,100 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
African / African-American	0.00534%	18,711
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.000847%	118,000

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.Arg415Trp
Coding: c.1243C>T
MANE Select: NM_003980
Type: single nucleotide variant
Location: chr6:136365765 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB
Residue 415: the 'disordered' region

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

Similar variants

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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-arg415trp (accessed [today's date]).

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