Is CUTA p.Pro50Ser (c.148C>T) pathogenic?

CUTA p.Pro50Ser (c.148C>T) is classified Uncertain significance in CUTA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.03%, amr).

How common is CUTA p.Pro50Ser (c.148C>T) in the general population?

CUTA p.Pro50Ser (c.148C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about CUTA p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

CUTA p.Pro50Ser

c.148C>T · VCV3270343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -5.45	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 7.5	GERP 1.9, phastCons 1
Overall
CADD	19.75	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

Grpmax group 0.03% Admixed American · 18/60,008 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00124% 20/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.47e-05%	1,180,034

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: CUTA
Protein: p.Pro50Ser
Coding: c.148C>T
MANE Select: NM_001014840
Type: single nucleotide variant
Location: chr6:33417590 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 2 PDB

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-pro50ser (accessed [today's date]).

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