Is CCDC136 p.Arg200Cys (c.598C>T) pathogenic?

CCDC136 p.Arg200Cys (c.598C>T) is classified Uncertain significance in CCDC136 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely pathogenic (0.5917); Very rare (popmax 0.0055%, sas).

How common is CCDC136 p.Arg200Cys (c.598C>T) in the general population?

CCDC136 p.Arg200Cys (c.598C>T) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about CCDC136 p.Arg200Cys (c.598C>T)?

AlphaMissense predicts likely pathogenic (score 0.5917) — an in-silico prediction, not a clinical call.

CCDC136 p.Arg200Cys

c.598C>T · VCV3263834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5917	likely pathogenic
REVEL	0.316	indeterminate
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 3e-06 · regional, not allelic
Overall
CADD	32.0	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 0.0055% South Asian · 5/90,958 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00192% 31/1,613,242 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,192
African / African-American	0.00267%	37,438
East Asian	0.00223%	44,872
European (non-Finnish)	0.00186%	53,622
Admixed American	0.00167%	59,954

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: CCDC136
Protein: p.Arg200Cys
Coding: c.598C>T
MANE Select: NM_022742
Type: single nucleotide variant
Location: chr7:128801437 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.24

Full CCDC136 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC136 p.Ala687= Benign ★★ same type
CCDC136 p.Asp218His Benign ★★ ⚠ same type
CCDC136 p.Glu1087= Benign ★★ same type
CCDC136 p.Glu1097Gly Likely benign ★★ ⚠ same type
CCDC136 p.Gly221= Benign ★★ same type
CCDC136 p.Gly980Arg Benign ★★ same type
CCDC136 p.Leu616= Benign ★★ same type
CCDC136 p.Val432Ile 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/ccdc136-p-arg200cys (accessed [today's date]).

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