Is SC5D p.Pro160Ser (c.478C>T) pathogenic?

SC5D p.Pro160Ser (c.478C>T) is classified Uncertain significance in SC5D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.3327); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SC5D p.Pro160Ser (c.478C>T)?

SC5D p.Pro160Ser (c.478C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SC5D p.Pro160Ser (c.478C>T) in the general population?

SC5D p.Pro160Ser (c.478C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about SC5D p.Pro160Ser (c.478C>T)?

AlphaMissense predicts likely benign (score 0.3327) — an in-silico prediction, not a clinical call.

SC5D p.Pro160Ser

c.478C>T · VCV3437690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3327	likely benign
REVEL	0.554	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP 1.8, phastCons 0.29
Regional constraint	o/e 0.85	unconstrained · MANE · 4,133 bp · p 0.0035 · regional, not allelic
Overall
CADD	21.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,032 alleles

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

Overall 0.000496% 8/1,614,036 alleles · very rare exomes 6/1,461,866 · genomes 2/152,170 · 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: SC5D
Protein: p.Pro160Ser
Coding: c.478C>T
MANE Select: NM_006918
Type: single nucleotide variant
Location: chr11:121307090 (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

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

Similar variants

SC5D p.Pro160Arg Pathogenic same residue
SC5D p.Asn292Ser Uncertain significance ★★ ⚠ same condition
SC5D p.Asp59Asn Uncertain significance ★★ ⚠ same condition
SC5D p.Met234Val Uncertain significance ★★ ⚠ same condition
SC5D p.Val57Leu Uncertain significance ★★ ⚠ same condition
SC5D p.Arg149His Conflicting classifications of pathogenicity ★ ⚠ same condition
SC5D p.Arg214Cys Uncertain significance ★ ⚠ same condition
SC5D p.Asp108Gly Conflicting classifications of pathogenicity ★ ⚠ 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-pro160ser (accessed [today's date]).

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