Is SNAPC4 p.Pro80Arg (c.239C>G) pathogenic?

SNAPC4 p.Pro80Arg (c.239C>G) is classified Uncertain significance in SNAPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.8276); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with SNAPC4 p.Pro80Arg (c.239C>G)?

SNAPC4 p.Pro80Arg (c.239C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SNAPC4 p.Pro80Arg (c.239C>G) in the general population?

SNAPC4 p.Pro80Arg (c.239C>G) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about SNAPC4 p.Pro80Arg (c.239C>G)?

AlphaMissense predicts likely pathogenic (score 0.8276) — an in-silico prediction, not a clinical call.

SNAPC4 p.Pro80Arg

c.239C>G · rs201209973 · VCV2228876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8276	likely pathogenic · top 9% in SNAPC4
REVEL	0.178	moderately benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 22 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	26.4	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 0.00668% East Asian · 3/44,900 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00167% 27/1,613,476 alleles · very rare exomes 23/1,461,192 · genomes 4/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,967
European (non-Finnish)	0.00195%	51,304
African / African-American	0.00133%	74,964

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.Pro80Arg
Coding: c.239C>G
MANE Select: NM_003086
dbSNP: rs201209973
Type: single nucleotide variant
Location: chr9:136395709 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.61 · 18 PDB
Residue 80: 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.Pro80Leu Uncertain significance ★ ⚠ same residue
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

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-pro80arg (accessed [today's date]).

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