Is SNAPC4 p.Pro148Arg (c.443C>G) pathogenic?

SNAPC4 p.Pro148Arg (c.443C>G) is classified Uncertain significance in SNAPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.965); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SNAPC4 p.Pro148Arg (c.443C>G)?

SNAPC4 p.Pro148Arg (c.443C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SNAPC4 p.Pro148Arg (c.443C>G) in the general population?

SNAPC4 p.Pro148Arg (c.443C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SNAPC4 p.Pro148Arg (c.443C>G)?

AlphaMissense predicts likely pathogenic (score 0.965) — an in-silico prediction, not a clinical call.

SNAPC4 p.Pro148Arg

c.443C>G · rs1274532207 · VCV2613491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.965	likely pathogenic · top 3% in SNAPC4
REVEL	0.54	indeterminate
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 22 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	26.5	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 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 6.2e-05% 1/1,613,564 alleles · very rare exomes 1/1,461,228 · genomes 0/152,336 · joint denominator

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.Pro148Arg
Coding: c.443C>G
MANE Select: NM_003086
dbSNP: rs1274532207
Type: single nucleotide variant
Location: chr9:136395326 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.61 · 18 PDB
Residue 148: 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-pro148arg (accessed [today's date]).

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