Is CCDC170 p.Asp4Glu (c.12C>A) pathogenic?

CCDC170 p.Asp4Glu (c.12C>A) is classified Uncertain significance in CCDC170 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely benign (0.1413); Rare (popmax 0.139%, afr).

How common is CCDC170 p.Asp4Glu (c.12C>A) in the general population?

CCDC170 p.Asp4Glu (c.12C>A) is rare (popmax 0.139%, afr) (gnomAD).

What do computational predictors say about CCDC170 p.Asp4Glu (c.12C>A)?

AlphaMissense predicts likely benign (score 0.1413) — an in-silico prediction, not a clinical call.

CCDC170 p.Asp4Glu

c.12C>A · rs372621574 · VCV2361839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1413 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.139%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1413	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.05	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 0.48	GERP -1.4, phastCons 0.004
Regional constraint	o/e 1.02	unconstrained · MANE · 124 kb · p 0.5 · regional, not allelic
Overall
CADD	3.825	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 0.139% African / African-American · 97/69,882 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0116% 176/1,513,604 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.139%	720
Admixed American	0.0318%	3,146
Remaining individualsnot grpmax-eligible	0.0239%	4,191
Middle Eastern	0.0199%	5,028
European (non-Finnish)	0.00431%	23,192

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.Asp4Glu
Coding: c.12C>A
MANE Select: NM_025059
dbSNP: rs372621574
Type: single nucleotide variant
Location: chr6:151494140 (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-asp4glu (accessed [today's date]).

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