Is CCDC97 p.Pro207His (c.620C>A) pathogenic?

CCDC97 p.Pro207His (c.620C>A) is classified Uncertain significance in CCDC97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.02%, nfe).

How common is CCDC97 p.Pro207His (c.620C>A) in the general population?

CCDC97 p.Pro207His (c.620C>A) is ultra-rare (popmax 0.02%, nfe) (gnomAD).

What do computational predictors say about CCDC97 p.Pro207His (c.620C>A)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

CCDC97 p.Pro207His

c.620C>A · rs752926768 · VCV2371757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.3
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	6.742	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% European (non-Finnish) · 236/1,179,852 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0151% 243/1,613,824 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.02%	4,999
Remaining individualsnot grpmax-eligible	0.008%	12,494
African / African-American	0.00267%	37,465

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.Pro207His
Coding: c.620C>A
MANE Select: NM_052848
dbSNP: rs752926768
Type: single nucleotide variant
Location: chr19:41319691 (GRCh38)
Gene constraint: LOEUF 1.149 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25
Residue 207: the 'disordered' region

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-pro207his (accessed [today's date]).

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