Is CCDC170 p.Ile676Phe (c.2026A>T) pathogenic?

CCDC170 p.Ile676Phe (c.2026A>T) is classified Uncertain significance in CCDC170 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.3455); Very rare (popmax 0.000339%, nfe).

How common is CCDC170 p.Ile676Phe (c.2026A>T) in the general population?

CCDC170 p.Ile676Phe (c.2026A>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CCDC170 p.Ile676Phe (c.2026A>T)?

AlphaMissense predicts ambiguous (score 0.3455) — an in-silico prediction, not a clinical call.

CCDC170 p.Ile676Phe

c.2026A>T · rs780980566 · VCV2253920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3455	ambiguous
REVEL	0.33	indeterminate
SaProt	LLR -8.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 124 kb · p 0.5 · regional, not allelic
Overall
CADD	16.42	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 0.000339% European (non-Finnish) · 4/1,180,026 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,036 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: CCDC170
Protein: p.Ile676Phe
Coding: c.2026A>T
MANE Select: NM_025059
dbSNP: rs780980566
Type: single nucleotide variant
Location: chr6:151618025 (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-ile676phe (accessed [today's date]).

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