Is DRC4 p.Asp239Tyr (c.715G>T) pathogenic?

DRC4 p.Asp239Tyr (c.715G>T) is classified Uncertain significance in DRC4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-15). AlphaMissense: likely pathogenic (0.7201); Very rare (popmax 0.00869%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DRC4 p.Asp239Tyr (c.715G>T)?

DRC4 p.Asp239Tyr (c.715G>T) is associated with Inborn genetic diseases, primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Asp239Tyr (c.715G>T) in the general population?

DRC4 p.Asp239Tyr (c.715G>T) is very rare (popmax 0.00869%, nfe) (gnomAD).

What do computational predictors say about DRC4 p.Asp239Tyr (c.715G>T)?

AlphaMissense predicts likely pathogenic (score 0.7201) — an in-silico prediction, not a clinical call.

DRC4 p.Asp239Tyr

c.715G>T · rs763326068 · VCV2159293

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00869%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7201	likely pathogenic · top 9% in DRC4
REVEL	0.353	indeterminate
SaProt	LLR -14.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00869% European (non-Finnish) · 102/1,174,240 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00679%

Overall 0.00668% 107/1,602,918 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00869%	11,512
Remaining individualsnot grpmax-eligible	0.00643%	15,540
East Asian	0.00225%	44,496

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: DRC4
Protein: p.Asp239Tyr
Coding: c.715G>T
MANE Select: NM_001481
dbSNP: rs763326068
Type: single nucleotide variant
Location: chr16:90036545 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 239: the 'microtubule-binding' region; a UniProt-annotated variant site (in cild33; loss of localization to cilia; abnormal cilia with axonemal disorganization)

Full DRC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 33

Similar variants

DRC4 p.Asp239Asn Uncertain significance ★ same residue
DRC4 p.Asp239= Likely benign ★ same residue
DRC4 c.495+1G>T Likely pathogenic ★★ same condition
DRC4 p.Gln357Ter Pathogenic ★★ same condition
DRC4 p.Ala280Thr Uncertain significance ★★ ⚠ same condition
DRC4 p.Ala460Pro Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg143Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg164Trp Uncertain significance ★★ ⚠ same condition

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/drc4-p-asp239tyr (accessed [today's date]).

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