Is SCD p.Ala292Ser (c.874G>T) pathogenic?

SCD p.Ala292Ser (c.874G>T) is classified Uncertain significance in SCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.2527); Absent from gnomAD v4.1.

How common is SCD p.Ala292Ser (c.874G>T) in the general population?

SCD p.Ala292Ser (c.874G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCD p.Ala292Ser (c.874G>T)?

AlphaMissense predicts likely benign (score 0.2527) — an in-silico prediction, not a clinical call.

SCD p.Ala292Ser

c.874G>T · VCV4581160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2527	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP 0.69
Regional constraint	o/e 0.55	unconstrained · MANE · 13 kb · p 4.2e-18 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: SCD
Protein: p.Ala292Ser
Coding: c.874G>T
MANE Select: NM_005063
Type: single nucleotide variant
Location: chr10:100356758 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.01 · 1 PDB
Residue 292: a β-strand

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

Similar variants

SCD p.Tyr308= Benign ★★ same type
SCD p.Ala328Val Uncertain significance ★ ⚠ same type
SCD p.Arg155Gly Uncertain significance ★ ⚠ same type
SCD p.Gln243His Uncertain significance ★ ⚠ same type
SCD p.Gln29Lys Uncertain significance ★ ⚠ same type
SCD p.Gly352Arg Uncertain significance ★ ⚠ same type
SCD p.Ile50Thr Uncertain significance ★ ⚠ same type
SCD p.Ile90Val 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/scd-p-ala292ser (accessed [today's date]).

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