Is CT83 p.Ser112Phe (c.335C>T) pathogenic?

CT83 p.Ser112Phe (c.335C>T) is classified Uncertain significance in CT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.1193); Rare (popmax 0.137%, mid).

How common is CT83 p.Ser112Phe (c.335C>T) in the general population?

CT83 p.Ser112Phe (c.335C>T) is rare (popmax 0.137%, mid) (gnomAD).

What do computational predictors say about CT83 p.Ser112Phe (c.335C>T)?

AlphaMissense predicts likely benign (score 0.1193) — an in-silico prediction, not a clinical call.

CT83 p.Ser112Phe

c.335C>T · rs201906931 · VCV2309653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1193 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.137%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1193	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.73	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 -0.042, phastCons 0.96
Regional constraint	o/e 0.94	unconstrained · MANE · 1,112 bp · p 0.6 · regional, not allelic
Overall
CADD	12.44	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 0.137% Middle Eastern · 6/4,370 alleles

Filtering AF 0.0598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0408%

Overall 0.00951% 115/1,209,174 alleles · rare exomes 108/1,097,509 · genomes 7/111,665 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.137%	728
South Asian	0.0212%	4,727
European (non-Finnish)	0.0103%	9,726
Admixed American	0.00657%	15,229
Remaining individualsnot grpmax-eligible	0.0042%	23,789

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.Ser112Phe
Coding: c.335C>T
MANE Select: NM_001017978
dbSNP: rs201906931
Type: single nucleotide variant
Location: chrX:116461748 (GRCh38)
Structure: AlphaFold pLDDT 71.69

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

Similar variants

CT83 p.Ala75Val Uncertain significance ★ ⚠ same type
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.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-ser112phe (accessed [today's date]).

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