Is CT83 p.Ala75Val (c.224C>T) pathogenic?

CT83 p.Ala75Val (c.224C>T) is classified Uncertain significance in CT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely benign (0.1642); Very rare (popmax 0.000671%, nfe).

How common is CT83 p.Ala75Val (c.224C>T) in the general population?

CT83 p.Ala75Val (c.224C>T) is very rare (popmax 0.000671%, nfe) (gnomAD).

What do computational predictors say about CT83 p.Ala75Val (c.224C>T)?

AlphaMissense predicts likely benign (score 0.1642) — an in-silico prediction, not a clinical call.

CT83 p.Ala75Val

c.224C>T · VCV3498036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000671%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1642	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.10	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 0.075	GERP -0.64
Regional constraint	o/e 0.94	unconstrained · MANE · 1,112 bp · p 0.6 · regional, not allelic
Overall
CADD	2.853	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 0.000671% European (non-Finnish) · 6/894,705 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000496% 6/1,208,756 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: CT83
Protein: p.Ala75Val
Coding: c.224C>T
MANE Select: NM_001017978
Type: single nucleotide variant
Location: chrX:116461859 (GRCh38)
Structure: AlphaFold pLDDT 71.69

Full CT83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CT83 p.Arg23His Uncertain significance ★ ⚠ same type
CT83 p.Arg64Trp Uncertain significance ★ ⚠ same type
CT83 p.Gln77His Uncertain significance ★ ⚠ same type
CT83 p.Ile74Thr Uncertain significance ★ ⚠ same type
CT83 p.Ile74Val Uncertain significance ★ ⚠ same type
CT83 p.Leu98Val Uncertain significance ★ ⚠ same type
CT83 p.Ser112Phe Uncertain significance ★ ⚠ same type
CT83 p.Ser9Asn 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/ct83-p-ala75val (accessed [today's date]).

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