Is CCDC170 p.Leu115Pro (c.344T>C) pathogenic?

CCDC170 p.Leu115Pro (c.344T>C) is classified Uncertain significance in CCDC170 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.5878); Very rare (popmax 0.00801%, afr).

How common is CCDC170 p.Leu115Pro (c.344T>C) in the general population?

CCDC170 p.Leu115Pro (c.344T>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CCDC170 p.Leu115Pro (c.344T>C)?

AlphaMissense predicts likely pathogenic (score 0.5878) — an in-silico prediction, not a clinical call.

CCDC170 p.Leu115Pro

c.344T>C · rs771908138 · VCV2476354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5878	likely pathogenic · top 4% in CCDC170
REVEL	0.287	benign-leaning
SaProt	LLR -14.38	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2, phastCons 0.94
Regional constraint	o/e 1.02	unconstrained · MANE · 124 kb · p 0.5 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,928 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000991% 16/1,613,822 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,488
European (non-Finnish)	0.000848%	117,990

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: CCDC170
Protein: p.Leu115Pro
Coding: c.344T>C
MANE Select: NM_025059
dbSNP: rs771908138
Type: single nucleotide variant
Location: chr6:151538202 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.06

Full CCDC170 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC170 p.Ala17Glu Uncertain significance ★ ⚠ same type
CCDC170 p.Ala17Val Uncertain significance ★ ⚠ same type
CCDC170 p.Ala246Ser Uncertain significance ★ ⚠ same type
CCDC170 p.Ala315Glu Uncertain significance ★ ⚠ same type
CCDC170 p.Ala331Val Uncertain significance ★ ⚠ same type
CCDC170 p.Ala694Asp Uncertain significance ★ ⚠ same type
CCDC170 p.Arg176Cys Uncertain significance ★ ⚠ same type
CCDC170 p.Arg198Gly 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/ccdc170-p-leu115pro (accessed [today's date]).

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