Is CTRC p.Ala184Ser (c.550G>T) pathogenic?

CTRC p.Ala184Ser (c.550G>T) is classified Uncertain significance in CTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.0996); Absent from gnomAD v4.1.

How common is CTRC p.Ala184Ser (c.550G>T) in the general population?

CTRC p.Ala184Ser (c.550G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTRC p.Ala184Ser (c.550G>T)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

CTRC p.Ala184Ser

c.550G>T · VCV3379418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -6.71	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 0.007	GERP -3.3
Regional constraint	o/e 0.90	unconstrained · MANE · 8,121 bp · p 0.049 · regional, not allelic
Overall
CADD	9.071	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: CTRC
Protein: p.Ala184Ser
Coding: c.550G>T
MANE Select: NM_007272
Type: single nucleotide variant
Location: chr1:15444662 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 184: a disulfide bond; the peptidase s1 domain; an α-helix

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

Similar variants

CTRC p.Ala184Val Uncertain significance ★★ ⚠ same residue
CTRC p.Ala184Gly Uncertain significance ★ ⚠ same residue
CTRC p.Ala184Pro Uncertain significance ★ ⚠ same residue
CTRC p.Ala184Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CTRC p.Ala184= Likely benign ★ same residue
CTRC c.494-1G>C Pathogenic/Likely pathogenic ★★ same type
CTRC p.Arg29Ter Pathogenic/Likely pathogenic ★★ same type
CTRC p.Gln174Ter Pathogenic/Likely pathogenic ★★ 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/ctrc-p-ala184ser (accessed [today's date]).

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