Is CYCS p.Ter106= (c.317A>G) pathogenic?

CYCS p.Ter106= (c.317A>G) is classified Likely benign in CYCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). Ultra-rare (popmax 0.0156%, eas).

How common is CYCS p.Ter106= (c.317A>G) in the general population?

CYCS p.Ter106= (c.317A>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

CYCS p.Ter106=

c.317A>G · VCV3728808

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	Δ0.22	donor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.6	GERP 1.9, phastCons 1
Overall
CADD	13.87	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,864 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000553% 8/1,447,294 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
South Asian	0.0011%	91,034

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: CYCS
Protein: p.Ter106=
Coding: c.317A>G
MANE Select: NM_018947
Type: single nucleotide variant
Location: chr7:25123702 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 97.95 · 13 PDB

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

Similar variants

CYCS p.Ter106Ser Uncertain significance ★ same residue
CYCS p.Gly42Ser Likely pathogenic ★★ same type
CYCS p.Ala52Thr Uncertain significance ★★ ⚠ same type
CYCS p.Leu33Val Uncertain significance ★★ ⚠ same type
CYCS c.-6T>G Benign/Likely benign ★★ same type
CYCS p.Ala51= Likely benign ★★ same type
CYCS p.Ile59= Likely benign ★★ same type
CYCS p.Pro72= Likely benign ★★ 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/cycs-p-ter106 (accessed [today's date]).

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