Is SGCD p.Phe85Leu (c.255C>G) pathogenic?

SGCD p.Phe85Leu (c.255C>G) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: likely pathogenic (0.9976); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Phe85Leu (c.255C>G)?

SGCD p.Phe85Leu (c.255C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SGCD p.Phe85Leu (c.255C>G) in the general population?

SGCD p.Phe85Leu (c.255C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Phe85Leu (c.255C>G)?

AlphaMissense predicts likely pathogenic (score 0.9976) — an in-silico prediction, not a clinical call.

SGCD p.Phe85Leu

c.255C>G · VCV3440551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9976	likely pathogenic · top 2% in SGCD
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 0.32, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	24.0	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 F84L vs ClinVar F85L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,252 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,694 alleles · very rare exomes 2/1,459,408 · genomes 0/152,286 · 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.Phe85Leu
Coding: c.255C>G
MANE Select: NM_000337
Type: single nucleotide variant
Location: chr5:156508663 (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.Phe85= Likely benign ★ 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
SGCD p.Asn268Ser 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-phe85leu (accessed [today's date]).

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