Is DRC2 p.Ala116Val (c.347C>T) pathogenic?

DRC2 p.Ala116Val (c.347C>T) is classified Uncertain significance in DRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.2145); Rare (popmax 0.103%, sas); Associated with primary ciliary dyskinesia 27.

What condition is associated with DRC2 p.Ala116Val (c.347C>T)?

DRC2 p.Ala116Val (c.347C>T) is associated with primary ciliary dyskinesia 27 (ClinVar).

How common is DRC2 p.Ala116Val (c.347C>T) in the general population?

DRC2 p.Ala116Val (c.347C>T) is rare (popmax 0.103%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DRC2 p.Ala116Val (c.347C>T)?

AlphaMissense predicts likely benign (score 0.2145) — an in-silico prediction, not a clinical call.

DRC2 p.Ala116Val

c.347C>T · rs563337831 · VCV474638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2145 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 27

Computational evidence

Protein change
AlphaMissense	0.2145	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -5.08	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.19 · regional, not allelic
Overall
CADD	24.9	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 0.103% South Asian · 94/91,068 alleles

Filtering AF 0.0863% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0801%

Overall 0.00638% 103/1,614,076 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.103%	969
Middle Eastern	0.0165%	6,050
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00167%	60,024
European (non-Finnish)	8.47e-05%	1,179,960

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.Ala116Val
Coding: c.347C>T
MANE Select: NM_033124
dbSNP: rs563337831
Type: single nucleotide variant
Location: chr12:48914450 (GRCh38)
Structure: AlphaFold pLDDT 83.21 · 1 PDB

Full DRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CCDC65 p.Arg70Gln Uncertain significance ★★ ⚠ same condition
CCDC65 p.Glu110Lys Uncertain significance ★★ ⚠ same condition
CCDC65 p.Lys158Asn Uncertain significance ★★ ⚠ same condition
DRC2 p.Ala109Val 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
DRC2 p.Arg315Gln 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-ala116val (accessed [today's date]).

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