Is CCDC136 p.Gln64Arg (c.191A>G) pathogenic?

CCDC136 p.Gln64Arg (c.191A>G) is classified Uncertain significance in CCDC136 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: ambiguous (0.4997); Very rare (popmax 0.00119%, sas).

How common is CCDC136 p.Gln64Arg (c.191A>G) in the general population?

CCDC136 p.Gln64Arg (c.191A>G) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about CCDC136 p.Gln64Arg (c.191A>G)?

AlphaMissense predicts ambiguous (score 0.4997) — an in-silico prediction, not a clinical call.

CCDC136 p.Gln64Arg

c.191A>G · rs2536346763 · VCV3138358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4997	ambiguous
REVEL	0.135	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 3e-06 · regional, not allelic
Overall
CADD	27.8	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 0.00119% South Asian · 1/84,112 alleles

Overall 7.14e-05% 1/1,401,168 alleles · very rare

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.Gln64Arg
Coding: c.191A>G
MANE Select: NM_022742
dbSNP: rs2536346763
Type: single nucleotide variant
Location: chr7:128794522 (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-gln64arg (accessed [today's date]).

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