Is SNCAIP p.Phe14Val (c.40T>G) pathogenic?

SNCAIP p.Phe14Val (c.40T>G) is classified Uncertain significance in SNCAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.9688); Absent from gnomAD v4.1.

How common is SNCAIP p.Phe14Val (c.40T>G) in the general population?

SNCAIP p.Phe14Val (c.40T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SNCAIP p.Phe14Val (c.40T>G)?

AlphaMissense predicts likely pathogenic (score 0.9688) — an in-silico prediction, not a clinical call.

SNCAIP p.Phe14Val

c.40T>G · VCV4587323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9688 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9688	likely pathogenic · top 8% in SNCAIP
REVEL	0.292	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 72 kb · p 0.00024 · 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

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: SNCAIP
Protein: p.Phe14Val
Coding: c.40T>G
MANE Select: NM_005460
Type: single nucleotide variant
Location: chr5:122391174 (GRCh38)
Gene constraint: LOEUF 0.636 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.98 · 1 PDB

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

Similar variants

SNCAIP p.Ala358Val Uncertain significance ★★ ⚠ same type
SNCAIP p.Ala363Thr Uncertain significance ★★ ⚠ same type
SNCAIP p.Glu237Lys Uncertain significance ★★ ⚠ same type
SNCAIP p.Leu148= Uncertain significance ★★ same type
SNCAIP p.Ser912Arg Uncertain significance ★★ ⚠ same type
SNCAIP p.Val461Ile Uncertain significance ★★ ⚠ same type
SNCAIP c.*103C>T Likely benign ★★ same type
SNCAIP c.*46T>G Likely benign ★★ same type

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/sncaip-p-phe14val (accessed [today's date]).

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