Is SCD p.Thr37Arg (c.110C>G) pathogenic?

SCD p.Thr37Arg (c.110C>G) is classified Uncertain significance in SCD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0609); Very rare (popmax 0.000254%, nfe).

How common is SCD p.Thr37Arg (c.110C>G) in the general population?

SCD p.Thr37Arg (c.110C>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about SCD p.Thr37Arg (c.110C>G)?

AlphaMissense predicts likely benign (score 0.0609) — an in-silico prediction, not a clinical call.

SCD p.Thr37Arg

c.110C>G · rs776589202 · VCV2244825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0609 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0609	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.55	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 0.9	GERP 0.51, phastCons 0.044
Regional constraint	o/e 0.87	unconstrained · MANE · 736 bp · p 0.23 · regional, not allelic
Overall
CADD	16.5	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 0.000254% European (non-Finnish) · 3/1,179,840 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,652 alleles · very rare

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.Thr37Arg
Coding: c.110C>G
MANE Select: NM_005063
dbSNP: rs776589202
Type: single nucleotide variant
Location: chr10:100348146 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.01 · 1 PDB

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-thr37arg (accessed [today's date]).

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