Is MAP7 p.Arg370Cys (c.1108C>T) pathogenic?

MAP7 p.Arg370Cys (c.1108C>T) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: ambiguous (0.4635); Very rare (popmax 0.005%, amr).

How common is MAP7 p.Arg370Cys (c.1108C>T) in the general population?

MAP7 p.Arg370Cys (c.1108C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about MAP7 p.Arg370Cys (c.1108C>T)?

AlphaMissense predicts ambiguous (score 0.4635) — an in-silico prediction, not a clinical call.

MAP7 p.Arg370Cys

c.1108C>T · VCV4103614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4635	ambiguous
REVEL	0.21	benign-leaning
SaProt	LLR -9.14	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 7.4	GERP 7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	27.7	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 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000743% 12/1,614,028 alleles · very rare exomes 9/1,461,886 · genomes 3/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00267%	37,452
East Asian	0.00223%	44,876
European (non-Finnish)	0.000339%	295,012

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.Arg370Cys
Coding: c.1108C>T
MANE Select: NM_003980
Type: single nucleotide variant
Location: chr6:136365900 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB
Residue 370: 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-arg370cys (accessed [today's date]).

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