Is SCD p.Ile90Val (c.268A>G) pathogenic?

SCD p.Ile90Val (c.268A>G) is classified Uncertain significance in SCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0748); Very rare (popmax 0.00802%, afr).

How common is SCD p.Ile90Val (c.268A>G) in the general population?

SCD p.Ile90Val (c.268A>G) is very rare (popmax 0.00802%, afr) (gnomAD).

What do computational predictors say about SCD p.Ile90Val (c.268A>G)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

SCD p.Ile90Val

c.268A>G · rs373888779 · VCV2462405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00802%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.04	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 -0.72	GERP -3.4
Regional constraint	o/e 0.55	unconstrained · MANE · 13 kb · p 4.2e-18 · regional, not allelic
Overall
CADD	16.54	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

Grpmax group 0.00802% African / African-American · 6/74,778 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,613,656 alleles · very rare exomes 1/1,461,740 · genomes 5/151,916 · joint denominator

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: SCD
Protein: p.Ile90Val
Coding: c.268A>G
MANE Select: NM_005063
dbSNP: rs373888779
Type: single nucleotide variant
Location: chr10:100348304 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.01 · 1 PDB
Residue 90: 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-ile90val (accessed [today's date]).

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