Is CYCS p.Thr103Ile (c.308C>T) pathogenic?

CYCS p.Thr103Ile (c.308C>T) is classified Conflicting classifications of pathogenicity in CYCS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-12-15). AlphaMissense: likely pathogenic (0.8963); Absent from gnomAD v4.1; Associated with thrombocytopenia 4.

What condition is associated with CYCS p.Thr103Ile (c.308C>T)?

CYCS p.Thr103Ile (c.308C>T) is associated with thrombocytopenia 4, thrombocytopenia (ClinVar).

How common is CYCS p.Thr103Ile (c.308C>T) in the general population?

CYCS p.Thr103Ile (c.308C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYCS p.Thr103Ile (c.308C>T)?

AlphaMissense predicts likely pathogenic (score 0.8963) — an in-silico prediction, not a clinical call.

CYCS p.Thr103Ile

c.308C>T · rs1583394618 · VCV627298

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

thrombocytopenia 4

Computational evidence

Protein change
AlphaMissense	0.8963	likely pathogenic
REVEL	0.527	indeterminate
SaProt	LLR -11.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 415 bp · p 0.00062 · regional, not allelic
Overall
CADD	25.2	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

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: CYCS
Protein: p.Thr103Ile
Coding: c.308C>T
MANE Select: NM_018947
dbSNP: rs1583394618
Type: single nucleotide variant
Location: chr7:25123711 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 97.95 · 13 PDB

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

Disease context

thrombocytopenia 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombocytopenia

Similar variants

CYCS p.Thr103Asn Uncertain significance ★ same residue
CYCS p.Gly42Ser Likely pathogenic ★★ same condition
CYCS p.Ala52Thr Uncertain significance ★★ ⚠ same condition
CYCS p.Leu33Val Uncertain significance ★★ ⚠ same condition
CYCS c.-6T>G Benign/Likely benign ★★ same condition
CYCS p.Ala97Asp Likely pathogenic ★ ⚠ same condition
CYCS p.Tyr49His Pathogenic ★ same condition
CYCS c.170-3T>C Conflicting classifications of pathogenicity ★ same condition

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/cycs-p-thr103ile (accessed [today's date]).

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