Is MAP7 p.Val194Ile (c.580G>A) pathogenic?

MAP7 p.Val194Ile (c.580G>A) is classified Uncertain significance in MAP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-20). AlphaMissense: likely benign (0.1188); Very rare (popmax 0.00789%, nfe).

How common is MAP7 p.Val194Ile (c.580G>A) in the general population?

MAP7 p.Val194Ile (c.580G>A) is very rare (popmax 0.00789%, nfe) (gnomAD).

What do computational predictors say about MAP7 p.Val194Ile (c.580G>A)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

MAP7 p.Val194Ile

c.580G>A · rs375908348 · VCV2539266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00789%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 206 kb · p 0.43 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00789% European (non-Finnish) · 93/1,178,452 alleles

Filtering AF 0.00657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00609%

Overall 0.00639% 103/1,610,864 alleles · very rare exomes 97/1,458,608 · genomes 6/152,256 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00789%	12,672
African / African-American	0.00401%	24,946
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,560
South Asian	0.00331%	30,185
Remaining individualsnot grpmax-eligible	0.0032%	31,204
East Asian	0.00224%	44,572

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.Val194Ile
Coding: c.580G>A
MANE Select: NM_003980
dbSNP: rs375908348
Type: single nucleotide variant
Location: chr6:136383728 (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.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-val194ile (accessed [today's date]).

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