Is DRC2 p.Ala109Val (c.326C>T) pathogenic?

DRC2 p.Ala109Val (c.326C>T) is classified Uncertain significance in DRC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-22). AlphaMissense: ambiguous (0.3575); Ultra-rare (popmax 0.0309%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DRC2 p.Ala109Val (c.326C>T)?

DRC2 p.Ala109Val (c.326C>T) is associated with Inborn genetic diseases, primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Ala109Val (c.326C>T) in the general population?

DRC2 p.Ala109Val (c.326C>T) is ultra-rare (popmax 0.0309%, nfe) (gnomAD).

What do computational predictors say about DRC2 p.Ala109Val (c.326C>T)?

AlphaMissense predicts ambiguous (score 0.3575) — an in-silico prediction, not a clinical call.

DRC2 p.Ala109Val

c.326C>T · rs139828323 · VCV970876

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3575 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0309%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3575	ambiguous
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.62, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	24.6	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 0.0309% European (non-Finnish) · 364/1,179,040 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0272%

Overall 0.0239% 386/1,612,684 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0309%	3,239
Remaining individualsnot grpmax-eligible	0.0208%	4,801
African / African-American	0.00533%	18,753
Finnishnot grpmax-eligible	0.00469%	21,329
Admixed American	0.00334%	29,964

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: DRC2
Protein: p.Ala109Val
Coding: c.326C>T
MANE Select: NM_033124
dbSNP: rs139828323
Type: single nucleotide variant
Location: chr12:48914429 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 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 27

Similar variants

DRC2 p.Ala109Ser Uncertain significance ★ ⚠ same residue
DRC2 p.Ala109= Likely benign ★ same residue
CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same condition
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala114Pro Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg118Cys Uncertain significance ★★ ⚠ same condition
DRC2 p.Arg294His 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/drc2-p-ala109val (accessed [today's date]).

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