Is SGCD p.Pro181Leu (c.542C>T) pathogenic?

SGCD p.Pro181Leu (c.542C>T) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-11). AlphaMissense: ambiguous (0.5258); No allele count reported in gnomAD v4.1 (AN 1,586,726); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Pro181Leu (c.542C>T)?

SGCD p.Pro181Leu (c.542C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SGCD p.Pro181Leu (c.542C>T) in the general population?

SGCD p.Pro181Leu (c.542C>T) is no allele count reported in gnomAD v4.1 (AN 1,586,726) (gnomAD).

What do computational predictors say about SGCD p.Pro181Leu (c.542C>T)?

AlphaMissense predicts ambiguous (score 0.5258) — an in-silico prediction, not a clinical call.

SGCD p.Pro181Leu

c.542C>T · VCV3440545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5258 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,726)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5258	ambiguous
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -12.41	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P180L vs ClinVar P181L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,586,726). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SGCD
Protein: p.Pro181Leu
Coding: c.542C>T
MANE Select: NM_000337
Type: single nucleotide variant
Location: chr5:156647503 (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.Pro181= Conflicting classifications of pathogenicity ★ same residue
SGCD p.Pro181Ser Uncertain significance ★ ⚠ same residue
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

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-pro181leu (accessed [today's date]).

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