Is CCDC97 p.Thr152Asn (c.455C>A) pathogenic?

CCDC97 p.Thr152Asn (c.455C>A) is classified Uncertain significance in CCDC97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: ambiguous (0.4784); Ultra-rare (popmax 0.0268%, afr).

How common is CCDC97 p.Thr152Asn (c.455C>A) in the general population?

CCDC97 p.Thr152Asn (c.455C>A) is ultra-rare (popmax 0.0268%, afr) (gnomAD).

What do computational predictors say about CCDC97 p.Thr152Asn (c.455C>A)?

AlphaMissense predicts ambiguous (score 0.4784) — an in-silico prediction, not a clinical call.

CCDC97 p.Thr152Asn

c.455C>A · VCV3997420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4784 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, afr)

Computational evidence

Protein change
AlphaMissense	0.4784	ambiguous
REVEL	0.443	indeterminate
SaProt	LLR -7.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	25.4	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 0.0268% African / African-American · 20/74,694 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.00131% 21/1,603,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0268%	3,735
European (non-Finnish)	8.53e-05%	1,171,663

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.Thr152Asn
Coding: c.455C>A
MANE Select: NM_052848
Type: single nucleotide variant
Location: chr19:41316792 (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.Ala121Pro Uncertain significance ★ ⚠ same type
CCDC97 p.Ala132Val Uncertain significance ★ ⚠ same type
CCDC97 p.Ala246Ser Uncertain significance ★ ⚠ same type
CCDC97 p.Arg110Cys Uncertain significance ★ ⚠ same type
CCDC97 p.Arg110His 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

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-thr152asn (accessed [today's date]).

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