Is CASD1 p.Ile404Phe (c.1210A>T) pathogenic?

CASD1 p.Ile404Phe (c.1210A>T) is classified Uncertain significance in CASD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1658); Very rare (popmax 0.00182%, nfe).

How common is CASD1 p.Ile404Phe (c.1210A>T) in the general population?

CASD1 p.Ile404Phe (c.1210A>T) is very rare (popmax 0.00182%, nfe) (gnomAD).

What do computational predictors say about CASD1 p.Ile404Phe (c.1210A>T)?

AlphaMissense predicts likely benign (score 0.1658) — an in-silico prediction, not a clinical call.

CASD1 p.Ile404Phe

c.1210A>T · VCV3827473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00182%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1658	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -7.54	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 9.3	GERP 1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 21 kb · p 0.00056 · regional, not allelic
Overall
CADD	23.2	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 0.00182% European (non-Finnish) · 21/1,151,992 alleles

Filtering AF 0.00117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000994%

Overall 0.00133% 21/1,582,608 alleles · very rare

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: CASD1
Protein: p.Ile404Phe
Coding: c.1210A>T
MANE Select: NM_022900
Type: single nucleotide variant
Location: chr7:94537838 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 87.87

Full CASD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SGCE p.Asp404Val Uncertain significance ★ ⚠ same residue
SGCE p.Asp404fs Pathogenic ★★ same residue
SGCE c.232+1G>T Pathogenic/Likely pathogenic ★★ same type
SGCE c.391-1G>A Pathogenic ★★ same type
SGCE c.825+1G>T Pathogenic/Likely pathogenic ★★ same type
SGCE p.Arg102Ter Pathogenic ★★ same type
SGCE p.Arg237Ter Pathogenic ★★ same type
SGCE p.Arg342Ter Pathogenic/Likely pathogenic ★★ 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/casd1-p-ile404phe (accessed [today's date]).

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