Is MAP7 p.Arg540Gly (c.1618C>G) pathogenic?

MAP7 p.Arg540Gly (c.1618C>G) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely benign (0.2124); Ultra-rare (popmax 0.0453%, afr).

How common is MAP7 p.Arg540Gly (c.1618C>G) in the general population?

MAP7 p.Arg540Gly (c.1618C>G) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about MAP7 p.Arg540Gly (c.1618C>G)?

AlphaMissense predicts likely benign (score 0.2124) — an in-silico prediction, not a clinical call.

MAP7 p.Arg540Gly

c.1618C>G · rs148141271 · VCV2388028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2124	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -12.49	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 1.2	GERP -0.96, phastCons 0.018
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	16.99	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 0.0453% African / African-American · 34/75,052 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.00274% 44/1,604,166 alleles · ultra-rare exomes 20/1,451,822 · genomes 24/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Admixed American	0.00836%	11,968
Remaining individualsnot grpmax-eligible	0.00801%	12,478

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.Arg540Gly
Coding: c.1618C>G
MANE Select: NM_003980
dbSNP: rs148141271
Type: single nucleotide variant
Location: chr6:136361088 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB
Residue 540: 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-arg540gly (accessed [today's date]).

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