Is CCDC97 p.Val63Leu (c.187G>T) pathogenic?

CCDC97 p.Val63Leu (c.187G>T) is classified Uncertain significance in CCDC97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1539); Ultra-rare (popmax 0.0113%, nfe).

How common is CCDC97 p.Val63Leu (c.187G>T) in the general population?

CCDC97 p.Val63Leu (c.187G>T) is ultra-rare (popmax 0.0113%, nfe) (gnomAD).

What do computational predictors say about CCDC97 p.Val63Leu (c.187G>T)?

AlphaMissense predicts likely benign (score 0.1539) — an in-silico prediction, not a clinical call.

CCDC97 p.Val63Leu

c.187G>T · rs143841115 · VCV2598816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1539 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1539	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	19.11	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 0.0113% European (non-Finnish) · 133/1,180,006 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00867% 140/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.219%	456
European (non-Finnish)grpmax	0.0113%	8,872
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,468
Admixed American	0.00167%	60,012

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val63Leu
Coding: c.187G>T
MANE Select: NM_052848
dbSNP: rs143841115
Type: single nucleotide variant
Location: chr19:41316524 (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-val63leu (accessed [today's date]).

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