Is CATSPERE p.Phe598Ser (c.1793T>C) pathogenic?

CATSPERE p.Phe598Ser (c.1793T>C) is classified Uncertain significance in CATSPERE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely benign (0.3387); Very rare (popmax 0.00801%, afr).

How common is CATSPERE p.Phe598Ser (c.1793T>C) in the general population?

CATSPERE p.Phe598Ser (c.1793T>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CATSPERE p.Phe598Ser (c.1793T>C)?

AlphaMissense predicts likely benign (score 0.3387) — an in-silico prediction, not a clinical call.

CATSPERE p.Phe598Ser

c.1793T>C · rs756075614 · VCV3137818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3387	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -4.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.61	GERP 1.6, phastCons 0.001
Regional constraint	o/e 0.87	unconstrained · MANE · 88 kb · p 8.1e-05 · regional, not allelic
Overall
CADD	17.49	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 0.00801% African / African-American · 6/74,932 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000558% 9/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,489
Remaining individualsnot grpmax-eligible	0.0032%	31,241
Admixed American	0.00167%	60,002

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: CATSPERE
Protein: p.Phe598Ser
Coding: c.1793T>C
MANE Select: NM_001130957
dbSNP: rs756075614
Type: single nucleotide variant
Location: chr1:244572615 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.01
Residue 598: a disulfide bond

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

Similar variants

ADSS2 p.Gly26Ala Uncertain significance ★ ⚠ same type
CATSPERE p.Asn535His Uncertain significance ★ ⚠ same type
CATSPERE p.Glu88Lys Uncertain significance ★ ⚠ same type
CATSPERE p.Ile630Thr Uncertain significance ★ ⚠ same type
CATSPERE p.Lys62Glu Uncertain significance ★ ⚠ same type
CATSPERE p.Arg948His Likely benign ★ 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/catspere-p-phe598ser (accessed [today's date]).

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