Is CAST p.Asp160Val (c.479A>T) pathogenic?

CAST p.Asp160Val (c.479A>T) is classified Uncertain significance in CAST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.084); Rare (popmax 0.222%, amr); Associated with Inborn genetic diseases.

What condition is associated with CAST p.Asp160Val (c.479A>T)?

CAST p.Asp160Val (c.479A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAST p.Asp160Val (c.479A>T) in the general population?

CAST p.Asp160Val (c.479A>T) is rare (popmax 0.222%, amr) (gnomAD).

What do computational predictors say about CAST p.Asp160Val (c.479A>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

CAST p.Asp160Val

c.479A>T · rs143562077 · VCV2056776

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.222%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -5.45	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 1.5	GERP 0.46, phastCons 0.97
Overall
CADD	11.82	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 D77V vs ClinVar D160V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.222% Admixed American · 133/59,998 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.0425% 681/1,603,814 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.222%	451
Ashkenazi Jewishnot grpmax-eligible	0.0474%	2,110
Remaining individualsnot grpmax-eligible	0.0466%	2,144
European (non-Finnish)	0.0417%	2,399
African / African-American	0.0214%	4,676
Middle Eastern	0.0166%	6,034

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: CAST
Protein: p.Asp160Val
Coding: c.479A>T
dbSNP: rs143562077
Type: single nucleotide variant
Location: chr5:96729655 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.67
Residue 160: the 'disordered' region

Full CAST 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

CAST p.Ala329Gly Uncertain significance ★★ ⚠ same condition
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CAST p.Glu296Gly Uncertain significance ★★ ⚠ same condition
CAST p.Ile274Val Uncertain significance ★★ ⚠ same condition
CAST p.Leu586Pro Uncertain significance ★★ ⚠ same condition
CAST p.Ser231Leu Uncertain significance ★★ ⚠ same condition
PCSK1 p.Asp176Asn Uncertain significance ★★ ⚠ same condition
PCSK1 p.Glu38Lys 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/cast-p-asp160val (accessed [today's date]).

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