Is SCD5 p.Phe151Cys (c.452T>G) pathogenic?

SCD5 p.Phe151Cys (c.452T>G) is classified Uncertain significance in SCD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely pathogenic (0.7226); Ultra-rare (popmax 0.0513%, eas).

How common is SCD5 p.Phe151Cys (c.452T>G) in the general population?

SCD5 p.Phe151Cys (c.452T>G) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

What do computational predictors say about SCD5 p.Phe151Cys (c.452T>G)?

AlphaMissense predicts likely pathogenic (score 0.7226) — an in-silico prediction, not a clinical call.

SCD5 p.Phe151Cys

c.452T>G · VCV4581161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7226 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7226	likely pathogenic
REVEL	0.626	indeterminate
SaProt	LLR -16.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 167 kb · p 0.0031 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0513% East Asian · 23/44,818 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0297%

Overall 0.0275% 444/1,613,586 alleles · ultra-rare exomes 390/1,461,892 · genomes 54/151,694 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.405%	247
East Asiangrpmax	0.0513%	1,949
Remaining individualsnot grpmax-eligible	0.0448%	2,232
South Asian	0.0319%	3,139
Admixed American	0.03%	3,329
African / African-American	0.0254%	3,939
European (non-Finnish)	0.0168%	5,959
Middle Eastern	0.0165%	6,062
Finnishnot grpmax-eligible	0.0125%	7,993

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SCD5
Protein: p.Phe151Cys
Coding: c.452T>G
MANE Select: NM_001037582
Type: single nucleotide variant
Location: chr4:82680824 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.99

Full SCD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCD5 p.Arg186Gly Uncertain significance ★★ ⚠ same type
SCD5 p.Ala16Ser Uncertain significance ★ ⚠ same type
SCD5 p.Ala22Asp Uncertain significance ★ ⚠ same type
SCD5 p.Ala78Val Uncertain significance ★ ⚠ same type
SCD5 p.Arg103Trp Uncertain significance ★ ⚠ same type
SCD5 p.Arg148His Uncertain significance ★ ⚠ same type
SCD5 p.Arg162Cys Uncertain significance ★ ⚠ same type
SCD5 p.Arg21Pro Uncertain significance ★ ⚠ 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/scd5-p-phe151cys (accessed [today's date]).

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