Is CUTC p.Leu213Phe (c.637C>T) pathogenic?

CUTC p.Leu213Phe (c.637C>T) is classified Uncertain significance in CUTC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: ambiguous (0.3474); Very rare (popmax 0.00133%, afr).

How common is CUTC p.Leu213Phe (c.637C>T) in the general population?

CUTC p.Leu213Phe (c.637C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CUTC p.Leu213Phe (c.637C>T)?

AlphaMissense predicts ambiguous (score 0.3474) — an in-silico prediction, not a clinical call.

CUTC p.Leu213Phe

c.637C>T · rs867119673 · VCV2568716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3474 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.3474	ambiguous
REVEL	0.308	indeterminate
SaProt	LLR -13.22	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.12 · regional, not allelic
Overall
CADD	25.8	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 0.00133% African / African-American · 1/75,006 alleles

Overall 0.000137% 2/1,461,288 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-Americangrpmax	0.00133%	75,006

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu213Phe
Coding: c.637C>T
MANE Select: NM_015960
dbSNP: rs867119673
Type: single nucleotide variant
Location: chr10:99754564 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.70 · 1 PDB
Residue 213: an α-helix

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-leu213phe (accessed [today's date]).

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