Is CCDC170 p.Ala331Val (c.992C>T) pathogenic?

CCDC170 p.Ala331Val (c.992C>T) is classified Uncertain significance in CCDC170 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.1074); Very rare (popmax 0.00267%, afr).

How common is CCDC170 p.Ala331Val (c.992C>T) in the general population?

CCDC170 p.Ala331Val (c.992C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CCDC170 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

CCDC170 p.Ala331Val

c.992C>T · VCV4220830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.71	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 1.3	GERP 0.46, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 124 kb · p 0.5 · regional, not allelic
Overall
CADD	17.43	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 0.00267% African / African-American · 2/74,910 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,455
European (non-Finnish)	0.000169%	590,016

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.Ala331Val
Coding: c.992C>T
MANE Select: NM_025059
Type: single nucleotide variant
Location: chr6:151573391 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.06
Residue 331: a UniProt-annotated variant site (in)

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.Ala694Asp Uncertain significance ★ ⚠ same type
CCDC170 p.Arg176Cys Uncertain significance ★ ⚠ same type
CCDC170 p.Arg198Gly Uncertain significance ★ ⚠ same type
CCDC170 p.Arg201His 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-ala331val (accessed [today's date]).

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