Is CCDC172 p.Leu52Pro (c.155T>C) pathogenic?

CCDC172 p.Leu52Pro (c.155T>C) is classified Uncertain significance in CCDC172 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely pathogenic (0.7402); Very rare (popmax 0.00134%, afr).

How common is CCDC172 p.Leu52Pro (c.155T>C) in the general population?

CCDC172 p.Leu52Pro (c.155T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CCDC172 p.Leu52Pro (c.155T>C)?

AlphaMissense predicts likely pathogenic (score 0.7402) — an in-silico prediction, not a clinical call.

CCDC172 p.Leu52Pro

c.155T>C · VCV4649305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7402	likely pathogenic · top 2% in CCDC172
REVEL	0.381	indeterminate
SaProt	LLR -12.70	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 54 kb · p 0.68 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00134% African / African-American · 1/74,884 alleles

Overall 0.000657% 1/152,218 alleles · very rare

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: CCDC172
Protein: p.Leu52Pro
Coding: c.155T>C
MANE Select: NM_198515
Type: single nucleotide variant
Location: chr10:116325378 (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.Arg33Ser 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

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-leu52pro (accessed [today's date]).

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