Is CYTH1 p.Ser190Phe (c.569C>T) pathogenic?

CYTH1 p.Ser190Phe (c.569C>T) is classified Uncertain significance in CYTH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely pathogenic (0.9988); Absent from gnomAD v4.1.

How common is CYTH1 p.Ser190Phe (c.569C>T) in the general population?

CYTH1 p.Ser190Phe (c.569C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYTH1 p.Ser190Phe (c.569C>T)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

CYTH1 p.Ser190Phe

c.569C>T · rs2544654902 · VCV3079813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic
REVEL	0.786	moderately pathogenic-leaning
SaProt	LLR -14.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 3,877 bp · p 4.6e-09 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CYTH1
Protein: p.Ser190Phe
Coding: c.569C>T
MANE Select: NM_004762
dbSNP: rs2544654902
Type: single nucleotide variant
Location: chr17:78698950 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.57 · 2 PDB
Residue 190: the sec7 domain; an α-helix

Full CYTH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYTH1 c.699+1G>C Uncertain significance ★ same type
CYTH1 p.Arg171Gln Uncertain significance ★ same type
CYTH1 p.Arg219Gln Uncertain significance ★ ⚠ same type
CYTH1 p.Arg313Gln Uncertain significance ★ ⚠ same type
CYTH1 p.Arg397Gln Uncertain significance ★ ⚠ same type
CYTH1 p.Asn123Asp Uncertain significance ★ ⚠ same type
CYTH1 p.Asn202Ser Uncertain significance ★ ⚠ same type
CYTH1 p.Asn204Ser Uncertain significance ★ ⚠ 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/cyth1-p-ser190phe (accessed [today's date]).

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