Is CT55 p.Ala166Ser (c.496G>T) pathogenic?

CT55 p.Ala166Ser (c.496G>T) is classified Uncertain significance in CT55 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.2989); Absent from gnomAD v4.1.

How common is CT55 p.Ala166Ser (c.496G>T) in the general population?

CT55 p.Ala166Ser (c.496G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CT55 p.Ala166Ser (c.496G>T)?

AlphaMissense predicts likely benign (score 0.2989) — an in-silico prediction, not a clinical call.

CT55 p.Ala166Ser

c.496G>T · rs1569481620 · VCV3078489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2989	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -8.51	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 -5.1	GERP -3.7
Regional constraint	o/e 0.80	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	13.29	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: CT55
Protein: p.Ala166Ser
Coding: c.496G>T
MANE Select: NM_001031705
dbSNP: rs1569481620
Type: single nucleotide variant
Location: chrX:135158240 (GRCh38)
Structure: AlphaFold pLDDT 75.60
Residue 166: a UniProt-annotated variant site (in spgfx7; protein undetectable in patient spermatozoa)

Full CT55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CT55 p.Ala166Thr Uncertain significance ★ ⚠ same residue
CT55 p.Ala104Ser Uncertain significance ★ ⚠ same type
CT55 p.Arg99Cys Uncertain significance ★ ⚠ same type
CT55 p.Asp149Asn Uncertain significance ★ ⚠ same type
CT55 p.Asp83Gly Uncertain significance ★ ⚠ same type
CT55 p.Glu152Lys Uncertain significance ★ ⚠ same type
CT55 p.Glu55Gly Uncertain significance ★ ⚠ same type
CT55 p.Ile161Phe 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/ct55-p-ala166ser (accessed [today's date]).

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