Is CTC1 p.Ser304Phe (c.911C>T) pathogenic?

CTC1 p.Ser304Phe (c.911C>T) is classified Uncertain significance in CTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). AlphaMissense: likely benign (0.1805); Absent from gnomAD v4.1.

How common is CTC1 p.Ser304Phe (c.911C>T) in the general population?

CTC1 p.Ser304Phe (c.911C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTC1 p.Ser304Phe (c.911C>T)?

AlphaMissense predicts likely benign (score 0.1805) — an in-silico prediction, not a clinical call.

CTC1 p.Ser304Phe

c.911C>T · rs1225861362 · VCV2663635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1805	likely benign
REVEL	0.477	indeterminate
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.088 · regional, not allelic
Overall
CADD	26.6	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

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: CTC1
Protein: p.Ser304Phe
Coding: c.911C>T
MANE Select: NM_025099
dbSNP: rs1225861362
Type: single nucleotide variant
Location: chr17:8236224 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 7 PDB

Full CTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTC1 p.Ser304Ala Uncertain significance ★★ ⚠ same residue
CTC1 p.Ser304= Likely benign ★ same residue
CTC1 p.Ser304Tyr Uncertain significance ⚠ same residue
CTC1 c.1617+5G>T Pathogenic/Likely pathogenic ★★ same type
CTC1 c.1818+1G>A Likely pathogenic ★★ same type
CTC1 c.2386-1G>A Likely pathogenic ★★ same type
CTC1 c.2758+1G>T Pathogenic/Likely pathogenic ★★ same type
CTC1 c.3221+1G>A Likely 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/ctc1-p-ser304phe (accessed [today's date]).

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