Is CDYL p.Arg58Cys (c.172C>T) pathogenic?

CDYL p.Arg58Cys (c.172C>T) is classified Uncertain significance in CDYL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.2005); Ultra-rare (popmax 0.0703%, sas).

How common is CDYL p.Arg58Cys (c.172C>T) in the general population?

CDYL p.Arg58Cys (c.172C>T) is ultra-rare (popmax 0.0703%, sas) (gnomAD).

What do computational predictors say about CDYL p.Arg58Cys (c.172C>T)?

AlphaMissense predicts likely benign (score 0.2005) — an in-silico prediction, not a clinical call.

CDYL p.Arg58Cys

c.172C>T · rs200651601 · VCV3141775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2005 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0703%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2005	likely benign
REVEL	0.529	indeterminate
SaProt	LLR -10.95	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 159 kb · p 0.037 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R112C vs ClinVar R58C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0703% South Asian · 64/91,076 alleles

Filtering AF 0.0565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.0242% 391/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.145%	688
South Asiangrpmax	0.0703%	1,423
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0256%	3,907
European (non-Finnish)	0.021%	4,758
African / African-American	0.0107%	9,375
Admixed American	0.01%	10,003
East Asian	0.00446%	22,435

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: CDYL
Protein: p.Arg58Cys
Coding: c.172C>T
MANE Select: NM_004824
dbSNP: rs200651601
Type: single nucleotide variant
Location: chr6:4891860 (GRCh38)
Gene constraint: LOEUF 0.293 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB
Residue 58: the 'disordered' region

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

Similar variants

CDYL p.Ala136Val Uncertain significance ★ ⚠ same type
CDYL p.Ala154Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala182Ser Uncertain significance ★ ⚠ same type
CDYL p.Ala183Val Uncertain significance ★ ⚠ same type
CDYL p.Ala195Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala329Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala527Ser Uncertain significance ★ ⚠ same type
CDYL p.Arg11Lys 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/cdyl-p-arg58cys (accessed [today's date]).

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