Is SGCD p.Pro253Thr (c.757C>A) pathogenic?

SGCD p.Pro253Thr (c.757C>A) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-28). AlphaMissense: likely benign (0.0623); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Pro253Thr (c.757C>A)?

SGCD p.Pro253Thr (c.757C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SGCD p.Pro253Thr (c.757C>A) in the general population?

SGCD p.Pro253Thr (c.757C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SGCD p.Pro253Thr (c.757C>A)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

SGCD p.Pro253Thr

c.757C>A · VCV3440546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -0.21, phastCons 0.98
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	13.39	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 P252T vs ClinVar P253T) — verify the residue.

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: SGCD
Protein: p.Pro253Thr
Coding: c.757C>A
MANE Select: NM_000337
Type: single nucleotide variant
Location: chr5:156759274 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SGCD p.Ala134Val Uncertain significance ★★ ⚠ same condition
SGCD p.Ala267Thr Uncertain significance ★★ ⚠ same condition
SGCD p.Arg11Trp Uncertain significance ★★ ⚠ same condition
SGCD p.Arg198Gln Uncertain significance ★★ ⚠ same condition
SGCD p.Arg270Lys Uncertain significance ★★ ⚠ same condition
SGCD p.Arg33Gln Uncertain significance ★★ ⚠ same condition
SGCD p.Asn268Ser Uncertain significance ★★ ⚠ same condition
SGCD p.Asp186Tyr Uncertain significance ★★ ⚠ same condition

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-pro253thr (accessed [today's date]).

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