Is CYCS p.Val84= (c.252C>T) pathogenic?

CYCS p.Val84= (c.252C>T) is classified Likely benign in CYCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). Very rare (popmax 0.00439%, sas).

How common is CYCS p.Val84= (c.252C>T) in the general population?

CYCS p.Val84= (c.252C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

CYCS p.Val84=

c.252C>T · rs759347650 · VCV2886603

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -1.9, phastCons 0.006
Overall
CADD	11.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,076 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00261% 42/1,610,954 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
South Asiangrpmax	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0032%	31,224
African / African-American	0.00134%	74,902
European (non-Finnish)	0.000763%	131,107

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val84=
Coding: c.252C>T
MANE Select: NM_018947
dbSNP: rs759347650
Type: single nucleotide variant
Location: chr7:25123767 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 97.95 · 13 PDB
Residue 84: an α-helix

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

Similar variants

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
CYCS p.Ala97Asp 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/cycs-p-val84 (accessed [today's date]).

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