Is CASD1 p.Ser584Phe (c.1751C>T) pathogenic?

CASD1 p.Ser584Phe (c.1751C>T) is classified Uncertain significance in CASD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: ambiguous (0.5226); Very rare (popmax 0.000509%, nfe).

How common is CASD1 p.Ser584Phe (c.1751C>T) in the general population?

CASD1 p.Ser584Phe (c.1751C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CASD1 p.Ser584Phe (c.1751C>T)?

AlphaMissense predicts ambiguous (score 0.5226) — an in-silico prediction, not a clinical call.

CASD1 p.Ser584Phe

c.1751C>T · VCV3827481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5226	ambiguous
REVEL	0.484	indeterminate
SaProt	LLR -11.45	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 21 kb · p 0.00056 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,178,370 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,459,158 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.Ser584Phe
Coding: c.1751C>T
MANE Select: NM_022900
Type: single nucleotide variant
Location: chr7:94549570 (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 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
SGCE p.Arg372Ter Pathogenic ★★ same type
SGCE p.Arg97Ter 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-ser584phe (accessed [today's date]).

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