Is CCDC97 p.Arg110Cys (c.328C>T) pathogenic?

CCDC97 p.Arg110Cys (c.328C>T) is classified Uncertain significance in CCDC97 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: ambiguous (0.5243); Ultra-rare (popmax 0.0173%, afr).

How common is CCDC97 p.Arg110Cys (c.328C>T) in the general population?

CCDC97 p.Arg110Cys (c.328C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about CCDC97 p.Arg110Cys (c.328C>T)?

AlphaMissense predicts ambiguous (score 0.5243) — an in-silico prediction, not a clinical call.

CCDC97 p.Arg110Cys

c.328C>T · rs75624130 · VCV2602788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5243 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Computational evidence

Protein change
AlphaMissense	0.5243	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -14.52	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.012 · 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 0.0173% African / African-American · 13/75,076 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00136% 22/1,614,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,775
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000593%	168,572

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: CCDC97
Protein: p.Arg110Cys
Coding: c.328C>T
MANE Select: NM_052848
dbSNP: rs75624130
Type: single nucleotide variant
Location: chr19:41316665 (GRCh38)
Gene constraint: LOEUF 1.149 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25

Full CCDC97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC97 p.Arg110His Uncertain significance ★ ⚠ same residue
CCDC97 p.Ala121Pro Uncertain significance ★ ⚠ same type
CCDC97 p.Ala132Val Uncertain significance ★ ⚠ same type
CCDC97 p.Ala246Ser Uncertain significance ★ ⚠ same type
CCDC97 p.Arg112Cys Uncertain significance ★ ⚠ same type
CCDC97 p.Arg112His Uncertain significance ★ ⚠ same type
CCDC97 p.Arg116His Uncertain significance ★ ⚠ same type
CCDC97 p.Arg116Leu 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/ccdc97-p-arg110cys (accessed [today's date]).

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