Is CCDC97 p.Arg146Trp (c.436C>T) pathogenic?

CCDC97 p.Arg146Trp (c.436C>T) is classified Uncertain significance in CCDC97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1428); Rare (popmax 0.177%, afr).

How common is CCDC97 p.Arg146Trp (c.436C>T) in the general population?

CCDC97 p.Arg146Trp (c.436C>T) is rare (popmax 0.177%, afr) (gnomAD).

What do computational predictors say about CCDC97 p.Arg146Trp (c.436C>T)?

AlphaMissense predicts likely benign (score 0.1428) — an in-silico prediction, not a clinical call.

CCDC97 p.Arg146Trp

c.436C>T · rs143157411 · VCV2537305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1428 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.177%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1428	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -9.84	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 1.8	GERP -0.79, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	24.9	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 0.177% African / African-American · 133/74,956 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.144%

Overall 0.0127% 205/1,609,012 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.177%	564
Remaining individualsnot grpmax-eligible	0.0257%	3,891
East Asian	0.0201%	4,964
Admixed American	0.0184%	5,447
South Asian	0.0055%	18,196
European (non-Finnish)	0.00255%	39,208
Finnishnot grpmax-eligible	0.00158%	63,490

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.Arg146Trp
Coding: c.436C>T
MANE Select: NM_052848
dbSNP: rs143157411
Type: single nucleotide variant
Location: chr19:41316773 (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-arg146trp (accessed [today's date]).

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