Is CUTC p.Ser252Phe (c.755C>T) pathogenic?

CUTC p.Ser252Phe (c.755C>T) is classified Uncertain significance in CUTC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.2336); Very rare (popmax 0.0011%, sas).

How common is CUTC p.Ser252Phe (c.755C>T) in the general population?

CUTC p.Ser252Phe (c.755C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CUTC p.Ser252Phe (c.755C>T)?

AlphaMissense predicts likely benign (score 0.2336) — an in-silico prediction, not a clinical call.

CUTC p.Ser252Phe

c.755C>T · VCV4236206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2336	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.12 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Overall 6.84e-05% 1/1,461,648 alleles · very rare

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: CUTC
Protein: p.Ser252Phe
Coding: c.755C>T
MANE Select: NM_015960
Type: single nucleotide variant
Location: chr10:99755672 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.70 · 1 PDB

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

Similar variants

COX15 c.-435C>T Benign ★★ same type
COX15 c.-472T>C Uncertain significance ★ same type
CUTC p.Ala13Pro Uncertain significance ★ ⚠ same type
CUTC p.Ala268Thr Uncertain significance ★ ⚠ same type
CUTC p.Ala46Asp Uncertain significance ★ ⚠ same type
CUTC p.Arg104Cys Uncertain significance ★ ⚠ same type
CUTC p.Arg104His Uncertain significance ★ ⚠ same type
CUTC p.Arg12Gly 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/cutc-p-ser252phe (accessed [today's date]).

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