Is CASD1 p.Ser650Phe (c.1949C>T) pathogenic?

CASD1 p.Ser650Phe (c.1949C>T) is classified Uncertain significance in CASD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely benign (0.1646); Very rare (popmax 0.0044%, afr).

How common is CASD1 p.Ser650Phe (c.1949C>T) in the general population?

CASD1 p.Ser650Phe (c.1949C>T) is very rare (popmax 0.0044%, afr) (gnomAD).

What do computational predictors say about CASD1 p.Ser650Phe (c.1949C>T)?

AlphaMissense predicts likely benign (score 0.1646) — an in-silico prediction, not a clinical call.

CASD1 p.Ser650Phe

c.1949C>T · rs957141169 · VCV3137487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1646	likely benign
REVEL	0.353	indeterminate
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,371 bp · p 0.026 · regional, not allelic
Overall
CADD	24.8	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 0.0044% African / African-American · 3/68,152 alleles

Filtering AF 0.00117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000624%

Overall 0.000274% 4/1,461,408 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0044%	22,717
Remaining individualsnot grpmax-eligible	0.00179%	55,964

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.Ser650Phe
Coding: c.1949C>T
MANE Select: NM_022900
dbSNP: rs957141169
Type: single nucleotide variant
Location: chr7:94551471 (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

CASD1 p.Ser650Cys Uncertain significance ★ ⚠ 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
SGCE p.Arg372Ter 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-ser650phe (accessed [today's date]).

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