Is SNAPC4 p.Val366Ile (c.1096G>A) pathogenic?

SNAPC4 p.Val366Ile (c.1096G>A) is classified Uncertain significance in SNAPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-28). AlphaMissense: likely benign (0.1593); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with SNAPC4 p.Val366Ile (c.1096G>A)?

SNAPC4 p.Val366Ile (c.1096G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SNAPC4 p.Val366Ile (c.1096G>A) in the general population?

SNAPC4 p.Val366Ile (c.1096G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about SNAPC4 p.Val366Ile (c.1096G>A)?

AlphaMissense predicts likely benign (score 0.1593) — an in-silico prediction, not a clinical call.

SNAPC4 p.Val366Ile

c.1096G>A · rs140560641 · VCV2370816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1593 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1593	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -7.07	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 1.7	GERP 1.5, phastCons 0.91
Regional constraint	o/e 1.13	unconstrained · MANE · 22 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	22.1	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 0.004% African / African-American · 3/74,934 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.0031% 50/1,613,350 alleles · very rare exomes 44/1,461,114 · genomes 6/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,978
European (non-Finnish)	0.00381%	26,220
South Asian	0.0022%	45,545

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: SNAPC4
Protein: p.Val366Ile
Coding: c.1096G>A
MANE Select: NM_003086
dbSNP: rs140560641
Type: single nucleotide variant
Location: chr9:136388471 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.61 · 18 PDB
Residue 366: the myb-like 2 domain; a β-strand

Full SNAPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SNAPC4 p.Ala1193Gly Uncertain significance ★★ ⚠ same condition
SNAPC4 p.Ala437Thr Uncertain significance ★★ ⚠ same condition
SNAPC4 p.Arg640Lys Uncertain significance ★★ ⚠ same condition
SNAPC4 p.Asp436Asn Uncertain significance ★★ ⚠ same condition
SNAPC4 p.Glu546Asp Uncertain significance ★★ ⚠ same condition
SNAPC4 p.Gly525Ser Likely benign ★★ same condition
SNAPC4 p.Ala1028Val Uncertain significance ★ ⚠ same condition
SNAPC4 p.Ala1046Thr Uncertain significance ★ ⚠ same condition

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/snapc4-p-val366ile (accessed [today's date]).

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