Is DRC1 p.Glu329Lys (c.985G>A) pathogenic?

DRC1 p.Glu329Lys (c.985G>A) is classified Uncertain significance in DRC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.4924); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DRC1 p.Glu329Lys (c.985G>A)?

DRC1 p.Glu329Lys (c.985G>A) is associated with Inborn genetic diseases, primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Glu329Lys (c.985G>A) in the general population?

DRC1 p.Glu329Lys (c.985G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DRC1 p.Glu329Lys (c.985G>A)?

AlphaMissense predicts ambiguous (score 0.4924) — an in-silico prediction, not a clinical call.

DRC1 p.Glu329Lys

c.985G>A · rs1060501406 · VCV407106

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4924	ambiguous
REVEL	0.356	indeterminate
SaProt	LLR -12.25	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	29.2	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 0.000254% European (non-Finnish) · 3/1,179,690 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,224 alleles · very rare

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: DRC1
Protein: p.Glu329Lys
Coding: c.985G>A
MANE Select: NM_145038
dbSNP: rs1060501406
Type: single nucleotide variant
Location: chr2:26440474 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 329: a UniProt-annotated variant site (in spgf80); a UniProt-annotated variant site (in cild21)

Full DRC1 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

Similar variants

DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Ser642Ter Pathogenic/Likely pathogenic ★★ same condition
DRC1 p.Ala250Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala391Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala416Gly Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala45Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala473Val 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/drc1-p-glu329lys (accessed [today's date]).

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