Is SCD p.Phe98Leu (c.294C>A) pathogenic?

SCD p.Phe98Leu (c.294C>A) is classified Likely benign in SCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.1508); Absent from gnomAD v4.1.

How common is SCD p.Phe98Leu (c.294C>A) in the general population?

SCD p.Phe98Leu (c.294C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCD p.Phe98Leu (c.294C>A)?

AlphaMissense predicts likely benign (score 0.1508) — an in-silico prediction, not a clinical call.

SCD p.Phe98Leu

c.294C>A · VCV3950711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1508 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1508	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -5.90	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 -0.26	GERP -3.1
Regional constraint	o/e 0.55	unconstrained · MANE · 13 kb · p 4.2e-18 · regional, not allelic
Overall
CADD	9.816	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: SCD
Protein: p.Phe98Leu
Coding: c.294C>A
MANE Select: NM_005063
Type: single nucleotide variant
Location: chr10:100348330 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.01 · 1 PDB
Residue 98: an α-helix

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

Similar variants

SCD p.Tyr308= Benign ★★ same type
SCD p.Ala292Ser Uncertain significance ★ ⚠ 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

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-phe98leu (accessed [today's date]).

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