Is SGCD p.Pro3Leu (c.8C>T) pathogenic?

SGCD p.Pro3Leu (c.8C>T) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-05). AlphaMissense: likely benign (0.1548); Very rare (popmax 0.000171%, nfe).

How common is SGCD p.Pro3Leu (c.8C>T) in the general population?

SGCD p.Pro3Leu (c.8C>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Pro3Leu (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1548) — an in-silico prediction, not a clinical call.

SGCD p.Pro3Leu

c.8C>T · rs1554094928 · VCV501190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1548	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.86	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	23.0	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 P2L vs ClinVar P3L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,168,310 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,583,026 alleles · very rare exomes 2/1,431,024 · genomes 0/152,002 · 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.Pro3Leu
Coding: c.8C>T
MANE Select: NM_000337
dbSNP: rs1554094928
Type: single nucleotide variant
Location: chr5:156344493 (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.Pro3= 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
SGCD c.294+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-pro3leu (accessed [today's date]).

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