Is CCDC175 p.Lys150Arg (c.449A>G) pathogenic?

CCDC175 p.Lys150Arg (c.449A>G) is classified Uncertain significance in CCDC175 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.0885); Very rare (popmax 0.00401%, amr).

How common is CCDC175 p.Lys150Arg (c.449A>G) in the general population?

CCDC175 p.Lys150Arg (c.449A>G) is very rare (popmax 0.00401%, amr) (gnomAD).

What do computational predictors say about CCDC175 p.Lys150Arg (c.449A>G)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

CCDC175 p.Lys150Arg

c.449A>G · rs1166897127 · VCV3138885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 0.6, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 72 kb · p 0.21 · regional, not allelic
Overall
CADD	15.42	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 0.00401% Admixed American · 2/49,888 alleles

Filtering AF 0.000786% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000623%

Overall 0.00124% 19/1,533,110 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00401%	24,944
Remaining individualsnot grpmax-eligible	0.00334%	29,942
European (non-Finnish)	0.00131%	76,395

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: CCDC175
Protein: p.Lys150Arg
Coding: c.449A>G
MANE Select: NM_001164399
dbSNP: rs1166897127
Type: single nucleotide variant
Location: chr14:59568287 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01

Full CCDC175 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC175 p.Ala124Thr Uncertain significance ★ ⚠ same type
CCDC175 p.Ala219Val Uncertain significance ★ ⚠ same type
CCDC175 p.Ala228Pro Uncertain significance ★ ⚠ same type
CCDC175 p.Ala316Val Uncertain significance ★ ⚠ same type
CCDC175 p.Ala353Pro Uncertain significance ★ ⚠ same type
CCDC175 p.Ala429Ser Uncertain significance ★ ⚠ same type
CCDC175 p.Arg122Gln Uncertain significance ★ ⚠ same type
CCDC175 p.Arg206Gly 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/ccdc175-p-lys150arg (accessed [today's date]).

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