Is CSAD p.Leu483Phe (c.1447C>T) pathogenic?

CSAD p.Leu483Phe (c.1447C>T) is classified Uncertain significance in CSAD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: ambiguous (0.3768); Absent from gnomAD v4.1.

How common is CSAD p.Leu483Phe (c.1447C>T) in the general population?

CSAD p.Leu483Phe (c.1447C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSAD p.Leu483Phe (c.1447C>T)?

AlphaMissense predicts ambiguous (score 0.3768) — an in-silico prediction, not a clinical call.

CSAD p.Leu483Phe

c.1447C>T · rs1938827495 · VCV2256126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3768 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3768	ambiguous
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -12.05	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -0.28, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 15 kb · p 0.2 · 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: CSAD
Protein: p.Leu483Phe
Coding: c.1447C>T
MANE Select: NM_001244705
dbSNP: rs1938827495
Type: single nucleotide variant
Location: chr12:53158546 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.67 · 1 PDB
Residue 483: an α-helix

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

Similar variants

CSAD p.Ala103= Benign ★★ same type
CSAD p.Ala199= Benign ★★ same type
CSAD p.Glu50= Benign ★★ same type
CSAD c.-21C>T Uncertain significance ★ same type
CSAD c.-24G>T Uncertain significance ★ same type
CSAD c.-27C>T Uncertain significance ★ same type
CSAD c.-33C>G Uncertain significance ★ same type
CSAD c.-48A>G Uncertain significance ★ 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/csad-p-leu483phe (accessed [today's date]).

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