Is SCD p.Tyr308= (c.924C>T) pathogenic?

SCD p.Tyr308= (c.924C>T) is classified Benign in SCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 7.23%, afr) — too common for a highly-penetrant pathogenic allele.

SCD p.Tyr308=

Q: How common is SCD p.Tyr308= (c.924C>T) in the general population?

SCD p.Tyr308= (c.924C>T) is common (popmax 7.23%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.924C>T · rs61732512 · VCV773538

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.23%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.9, phastCons 1
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.23% African / African-American · 5,427/75,016 alleles

Filtering AF 7.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.01%

Overall 0.41% 6,616/1,613,978 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.23%	14
Admixed American	0.648%	154
Remaining individualsnot grpmax-eligible	0.61%	164
Middle Eastern	0.528%	189
European (non-Finnish)	0.0306%	3,268
South Asian	0.0231%	4,337
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
Finnishnot grpmax-eligible	0.00468%	21,348

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.Tyr308=
Coding: c.924C>T
MANE Select: NM_005063
dbSNP: rs61732512
Type: single nucleotide variant
Location: chr10:100360777 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.01 · 1 PDB
Residue 308: a β-strand

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

Similar variants

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
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-tyr308 (accessed [today's date]).

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