Is CCDC172 p.Arg33Ser (c.99A>C) pathogenic?

CCDC172 p.Arg33Ser (c.99A>C) is classified Uncertain significance in CCDC172 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.2025); Absent from gnomAD v4.1.

How common is CCDC172 p.Arg33Ser (c.99A>C) in the general population?

CCDC172 p.Arg33Ser (c.99A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC172 p.Arg33Ser (c.99A>C)?

AlphaMissense predicts likely benign (score 0.2025) — an in-silico prediction, not a clinical call.

CCDC172 p.Arg33Ser

c.99A>C · VCV3996736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2025 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2025	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -4.86	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 0.51	GERP 2.2, phastCons 0.72
Regional constraint	o/e 1.02	unconstrained · MANE · 54 kb · p 0.68 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC172
Protein: p.Arg33Ser
Coding: c.99A>C
MANE Select: NM_198515
Type: single nucleotide variant
Location: chr10:116325322 (GRCh38)
Gene constraint: LOEUF 1.536 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.63

Full CCDC172 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC172 p.Ala75Asp Uncertain significance ★ ⚠ same type
CCDC172 p.Ala75Thr Uncertain significance ★ ⚠ same type
CCDC172 p.Arg35Cys Uncertain significance ★ ⚠ same type
CCDC172 p.Asp114Asn Uncertain significance ★ ⚠ same type
CCDC172 p.Asp230Asn Uncertain significance ★ ⚠ same type
CCDC172 p.Gln100His Uncertain significance ★ ⚠ same type
CCDC172 p.Gln100Pro Uncertain significance ★ ⚠ same type
CCDC172 p.Gln160Arg 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/ccdc172-p-arg33ser (accessed [today's date]).

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