Is CUTA p.Ser172Cys (c.515C>G) pathogenic?

CUTA p.Ser172Cys (c.515C>G) is classified Uncertain significance in CUTA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1136); Absent from gnomAD v4.1.

How common is CUTA p.Ser172Cys (c.515C>G) in the general population?

CUTA p.Ser172Cys (c.515C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUTA p.Ser172Cys (c.515C>G)?

AlphaMissense predicts likely benign (score 0.1136) — an in-silico prediction, not a clinical call.

CUTA p.Ser172Cys

c.515C>G · VCV4236195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1136 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1136	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.7, phastCons 0.12
Overall
CADD	22.1	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: CUTA
Protein: p.Ser172Cys
Coding: c.515C>G
MANE Select: NM_001014840
Type: single nucleotide variant
Location: chr6:33416675 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 2 PDB
Residue 172: the 'o-glycosylated at one site' region

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-ser172cys (accessed [today's date]).

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