Is CUTA p.Ser69Phe (c.206C>T) pathogenic?

CUTA p.Ser69Phe (c.206C>T) is classified Uncertain significance in CUTA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-21). AlphaMissense: likely pathogenic (0.9161); Absent from gnomAD v4.1.

How common is CUTA p.Ser69Phe (c.206C>T) in the general population?

CUTA p.Ser69Phe (c.206C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUTA p.Ser69Phe (c.206C>T)?

AlphaMissense predicts likely pathogenic (score 0.9161) — an in-silico prediction, not a clinical call.

CUTA p.Ser69Phe

c.206C>T · VCV4008394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9161 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9161	likely pathogenic
REVEL	0.486	indeterminate
SaProt	LLR -15.35	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 12	GERP 1.8, phastCons 1
Overall
CADD	32.0	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: CUTA
Protein: p.Ser69Phe
Coding: c.206C>T
MANE Select: NM_001014840
Type: single nucleotide variant
Location: chr6:33417532 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 2 PDB
Residue 69: a β-strand

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

Similar variants

CUTA c.44C>A Uncertain significance ★ same type
CUTA p.Ala12Val Uncertain significance ★ same type
CUTA p.Ala94Thr Uncertain significance ★ ⚠ same type
CUTA p.Arg138Cys Uncertain significance ★ ⚠ same type
CUTA p.Arg165Cys Uncertain significance ★ ⚠ same type
CUTA p.Asn98Ile Uncertain significance ★ ⚠ same type
CUTA p.Glu144Lys Uncertain significance ★ ⚠ same type
CUTA p.Gly10Glu 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/cuta-p-ser69phe (accessed [today's date]).

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