Is CAST p.Ile190Val (c.568A>G) pathogenic?

CAST p.Ile190Val (c.568A>G) is classified Conflicting classifications of pathogenicity in CAST (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0735%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAST p.Ile190Val (c.568A>G)?

CAST p.Ile190Val (c.568A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CAST p.Ile190Val (c.568A>G) in the general population?

CAST p.Ile190Val (c.568A>G) is ultra-rare (popmax 0.0735%, nfe) (gnomAD).

What do computational predictors say about CAST p.Ile190Val (c.568A>G)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CAST p.Ile190Val

c.568A>G · rs142144208 · VCV1492002

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -4.93	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 -2.6	GERP -3.8
Overall
CADD	0.003	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 I107V vs ClinVar I190V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0735% European (non-Finnish) · 867/1,179,824 alleles

Filtering AF 0.0694% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0678%

Overall 0.0566% 914/1,613,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0735%	1,361
Remaining individualsnot grpmax-eligible	0.0384%	2,603
Admixed American	0.02%	5,000
Middle Eastern	0.0164%	6,084
Finnishnot grpmax-eligible	0.00625%	16,009
African / African-American	0.004%	24,969
South Asian	0.00329%	30,363

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.Ile190Val
Coding: c.568A>G
dbSNP: rs142144208
Type: single nucleotide variant
Location: chr5:96730798 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.67

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
CAST p.Asp160Val Uncertain significance ★★ ⚠ same condition
CAST p.Gln731His Uncertain significance ★★ ⚠ same condition
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

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-ile190val (accessed [today's date]).

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