Is SGCD p.Ala238Ser (c.712G>T) pathogenic?

SGCD p.Ala238Ser (c.712G>T) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-14). AlphaMissense: likely benign (0.1082); Very rare (popmax 0.00133%, afr).

How common is SGCD p.Ala238Ser (c.712G>T) in the general population?

SGCD p.Ala238Ser (c.712G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about SGCD p.Ala238Ser (c.712G>T)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

SGCD p.Ala238Ser

c.712G>T · rs1757448747 · VCV2435902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.432	indeterminate
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	22.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A237S vs ClinVar A238S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,050 alleles

Overall 6.2e-05% 1/1,613,628 alleles · very rare exomes 1/1,461,306 · genomes 0/152,322 · 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: SGCD
Protein: p.Ala238Ser
Coding: c.712G>T
MANE Select: NM_000337
dbSNP: rs1757448747
Type: single nucleotide variant
Location: chr5:156759229 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 81.43

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

Similar variants

SGCD p.Ala238Thr Uncertain significance ★ ⚠ same residue
SGCD p.Ala238= Likely benign ★ same residue
SGCD p.Arg165Ter Pathogenic ★★★ same type
SGCD p.Arg97Ter Pathogenic ★★★ same type
SGCD p.Arg31Gly Uncertain significance ★★★ ⚠ same type
SGCD p.Arg31Trp Uncertain significance ★★★ ⚠ same type
SGCD p.Ile64Thr Uncertain significance ★★★ ⚠ same type
SGCD c.192+1G>A Likely pathogenic ★★ 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/sgcd-p-ala238ser (accessed [today's date]).

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