Is SNAPC4 p.Pro83Ser (c.247C>T) pathogenic?

SNAPC4 p.Pro83Ser (c.247C>T) is classified Uncertain significance in SNAPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.7217); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SNAPC4 p.Pro83Ser (c.247C>T)?

SNAPC4 p.Pro83Ser (c.247C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SNAPC4 p.Pro83Ser (c.247C>T) in the general population?

SNAPC4 p.Pro83Ser (c.247C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SNAPC4 p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely pathogenic (score 0.7217) — an in-silico prediction, not a clinical call.

SNAPC4 p.Pro83Ser

c.247C>T · rs2538766069 · VCV2297110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7217 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7217	likely pathogenic
REVEL	0.12	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 0.25, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 22 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SNAPC4
Protein: p.Pro83Ser
Coding: c.247C>T
MANE Select: NM_003086
dbSNP: rs2538766069
Type: single nucleotide variant
Location: chr9:136395701 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.61 · 18 PDB

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-pro83ser (accessed [today's date]).

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