Is MAP7 p.Arg159His (c.476G>A) pathogenic?

MAP7 p.Arg159His (c.476G>A) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.3085); Ultra-rare (popmax 0.0443%, nfe).

How common is MAP7 p.Arg159His (c.476G>A) in the general population?

MAP7 p.Arg159His (c.476G>A) is ultra-rare (popmax 0.0443%, nfe) (gnomAD).

What do computational predictors say about MAP7 p.Arg159His (c.476G>A)?

AlphaMissense predicts likely benign (score 0.3085) — an in-silico prediction, not a clinical call.

MAP7 p.Arg159His

c.476G>A · rs148680029 · VCV2221885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3085 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0443%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3085	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -12.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	26.9	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 0.0443% European (non-Finnish) · 523/1,180,014 alleles

Filtering AF 0.0412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0399%

Overall 0.0432% 698/1,614,138 alleles · ultra-rare exomes 640/1,461,834 · genomes 58/152,304 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.345%	290
Remaining individualsnot grpmax-eligible	0.0512%	1,953
European (non-Finnish)grpmax	0.0443%	2,256
South Asian	0.0198%	5,060
Finnishnot grpmax-eligible	0.0156%	6,403
East Asian	0.0111%	8,976
African / African-American	0.00933%	10,720
Admixed American	0.00167%	60,020

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg159His
Coding: c.476G>A
MANE Select: NM_003980
dbSNP: rs148680029
Type: single nucleotide variant
Location: chr6:136388443 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB
Residue 159: the 'disordered' region

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

Similar variants

MAP7 p.Arg159Cys Uncertain significance ★ ⚠ same residue
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

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-arg159his (accessed [today's date]).

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