Is CTBS p.Phe118Ser (c.353T>C) pathogenic?

CTBS p.Phe118Ser (c.353T>C) is classified Likely benign in CTBS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: likely benign (0.1052); Ultra-rare (popmax 0.016%, afr).

How common is CTBS p.Phe118Ser (c.353T>C) in the general population?

CTBS p.Phe118Ser (c.353T>C) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about CTBS p.Phe118Ser (c.353T>C)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

CTBS p.Phe118Ser

c.353T>C · rs756387712 · VCV2609155

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -5.18	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 5.3	GERP 0.63, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.43 · regional, not allelic
Overall
CADD	16.45	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,908 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00093% 15/1,613,316 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
Remaining individualsnot grpmax-eligible	0.0032%	31,222
East Asian	0.00223%	44,792

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: CTBS
Protein: p.Phe118Ser
Coding: c.353T>C
MANE Select: NM_004388
dbSNP: rs756387712
Type: single nucleotide variant
Location: chr1:84570103 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.87
Residue 118: the gh18 domain

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

Similar variants

CTBS p.Asn357= Benign ★★ same type
CTBS p.Ala284Thr Uncertain significance ★ ⚠ same type
CTBS p.Ala32Val Uncertain significance ★ ⚠ same type
CTBS p.Arg169Ser Uncertain significance ★ ⚠ same type
CTBS p.Arg189Gly Uncertain significance ★ ⚠ same type
CTBS p.Arg277Gln Uncertain significance ★ ⚠ same type
CTBS p.Arg287Cys Uncertain significance ★ ⚠ same type
CTBS p.Arg349Gln 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/ctbs-p-phe118ser (accessed [today's date]).

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