Is SC5D p.Pro160Arg (c.479C>G) pathogenic?

SC5D p.Pro160Arg (c.479C>G) is classified Pathogenic in SC5D (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-06-02). AlphaMissense: likely pathogenic (0.9219); Ultra-rare (popmax 0.0165%, mid); Associated with lathosterolosis.

What condition is associated with SC5D p.Pro160Arg (c.479C>G)?

SC5D p.Pro160Arg (c.479C>G) is associated with lathosterolosis (ClinVar).

How common is SC5D p.Pro160Arg (c.479C>G) in the general population?

SC5D p.Pro160Arg (c.479C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Lathosterolosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SC5D p.Pro160Arg (c.479C>G)?

AlphaMissense predicts likely pathogenic (score 0.9219) — an in-silico prediction, not a clinical call.

SC5D p.Pro160Arg

c.479C>G · rs1947971579 · VCV916042

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9219 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lathosterolosis

Computational evidence

Protein change
AlphaMissense	0.9219	likely pathogenic ✓ concordant with ClinVar
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -14.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 0.86
Regional constraint	o/e 0.85	unconstrained · MANE · 4,133 bp · p 0.0035 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,614,140 alleles · ultra-rare exomes 9/1,461,860 · genomes 0/152,280 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.000678%	147,502

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: SC5D
Protein: p.Pro160Arg
Coding: c.479C>G
MANE Select: NM_006918
dbSNP: rs1947971579
Type: single nucleotide variant
Location: chr11:121307091 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.05
Residue 160: the fatty acid hydroxylase domain

Full SC5D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lathosterolosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lathosterolosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

SC5D p.Pro160Ser Uncertain significance ★ ⚠ same residue
SC5D p.Asn292Ser Uncertain significance ★★ ⚠ same condition
SC5D p.Lys148Glu Uncertain significance ★★ ⚠ same condition
SC5D c.211-8A>T Benign/Likely benign ★★ same condition
SC5D c.343+3A>G Likely benign ★★ same condition
SC5D c.*1328C>T Benign ★★ same condition
SC5D c.*81A>C Benign ★★ same condition
SC5D p.Ile182Val Benign ★★ 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/sc5d-p-pro160arg (accessed [today's date]).

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