Is MAP7 p.Arg214Cys (c.640C>T) pathogenic?

MAP7 p.Arg214Cys (c.640C>T) is classified Uncertain significance in MAP7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.3863); Very rare (popmax 0.005%, amr).

How common is MAP7 p.Arg214Cys (c.640C>T) in the general population?

MAP7 p.Arg214Cys (c.640C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about MAP7 p.Arg214Cys (c.640C>T)?

AlphaMissense predicts ambiguous (score 0.3863) — an in-silico prediction, not a clinical call.

MAP7 p.Arg214Cys

c.640C>T · VCV4103608

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3863 · 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	0.3863	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -9.87	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	32.0	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 · 3/60,004 alleles

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

Overall 0.000683% 11/1,610,178 alleles · very rare exomes 11/1,457,908 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
East Asian	0.00446%	22,416
Remaining individualsnot grpmax-eligible	0.0016%	62,362
South Asian	0.0011%	90,984
European (non-Finnish)	0.00034%	294,184

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.Arg214Cys
Coding: c.640C>T
MANE Select: NM_003980
Type: single nucleotide variant
Location: chr6:136377866 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 1 PDB

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

Similar variants

MAP7 p.Arg214His Uncertain significance ★ ⚠ same residue
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-arg214cys (accessed [today's date]).

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