Is CCDC174 p.Val466Met (c.1396G>A) pathogenic?

CCDC174 p.Val466Met (c.1396G>A) is classified Likely benign in CCDC174 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.2066); Rare (popmax 0.546%, eas).

How common is CCDC174 p.Val466Met (c.1396G>A) in the general population?

CCDC174 p.Val466Met (c.1396G>A) is rare (popmax 0.546%, eas) (gnomAD).

What do computational predictors say about CCDC174 p.Val466Met (c.1396G>A)?

AlphaMissense predicts likely benign (score 0.2066) — an in-silico prediction, not a clinical call.

CCDC174 p.Val466Met

c.1396G>A · rs79022832 · VCV731345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2066 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.546%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2066	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.66	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 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.15 · regional, not allelic
Overall
CADD	24.1	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 0.546% East Asian · 244/44,716 alleles

Filtering AF 0.489% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.468%

Overall 0.0188% 302/1,607,790 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.546%	183
South Asian	0.0474%	2,111
Remaining individualsnot grpmax-eligible	0.0209%	4,785
European (non-Finnish)	0.00017%	587,672

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: CCDC174
Protein: p.Val466Met
Coding: c.1396G>A
MANE Select: NM_016474
dbSNP: rs79022832
Type: single nucleotide variant
Location: chr3:14671186 (GRCh38)
Gene constraint: LOEUF 0.926 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79

Full CCDC174 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC174 p.Asp395His Uncertain significance ★★ ⚠ same type
CCDC174 p.Phe29Ser Uncertain significance ★★ ⚠ same type
CCDC174 p.Pro158Ser Uncertain significance ★★ ⚠ same type
CCDC174 c.1106-10T>A Benign/Likely benign ★★ same type
CCDC174 c.308-55C>A Benign ★★ same type
CCDC174 c.485+47G>A Benign ★★ same type
CCDC174 c.485+83C>G Benign ★★ same type
CCDC174 c.485+83C>T Benign ★★ 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/ccdc174-p-val466met (accessed [today's date]).

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