Is SNAPC4 p.Pro594Ser (c.1780C>T) pathogenic?

SNAPC4 p.Pro594Ser (c.1780C>T) is classified Uncertain significance in SNAPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0806); Ultra-rare (popmax 0.0188%, afr); Associated with Inborn genetic diseases.

What condition is associated with SNAPC4 p.Pro594Ser (c.1780C>T)?

SNAPC4 p.Pro594Ser (c.1780C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SNAPC4 p.Pro594Ser (c.1780C>T) in the general population?

SNAPC4 p.Pro594Ser (c.1780C>T) is ultra-rare (popmax 0.0188%, afr) (gnomAD).

What do computational predictors say about SNAPC4 p.Pro594Ser (c.1780C>T)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

SNAPC4 p.Pro594Ser

c.1780C>T · rs904849527 · VCV3166904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -2
Regional constraint	o/e 1.13	unconstrained · MANE · 22 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	1.08	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 0.0188% African / African-American · 14/74,274 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00912%

Overall 0.000945% 15/1,587,236 alleles · ultra-rare exomes 8/1,434,992 · genomes 7/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0188%	5,305
European (non-Finnish)	8.57e-05%	1,166,978

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.Pro594Ser
Coding: c.1780C>T
MANE Select: NM_003086
dbSNP: rs904849527
Type: single nucleotide variant
Location: chr9:136383389 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.61 · 18 PDB
Residue 594: the 'disordered' region

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-pro594ser (accessed [today's date]).

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