Is DRC1 p.Ala9Val (c.26C>T) pathogenic?

DRC1 p.Ala9Val (c.26C>T) is classified Conflicting classifications of pathogenicity in DRC1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0677); Rare (popmax 0.347%, mid); Associated with Inborn genetic diseases.

What condition is associated with DRC1 p.Ala9Val (c.26C>T)?

DRC1 p.Ala9Val (c.26C>T) is associated with Inborn genetic diseases, primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Ala9Val (c.26C>T) in the general population?

DRC1 p.Ala9Val (c.26C>T) is rare (popmax 0.347%, mid) (gnomAD).

What do computational predictors say about DRC1 p.Ala9Val (c.26C>T)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

DRC1 p.Ala9Val

c.26C>T · rs146049908 · VCV571634

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.347%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.22	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 -0.096	GERP -4.7, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	0.48	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 0.347% Middle Eastern · 21/6,056 alleles

Filtering AF 0.232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.035% 564/1,610,364 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.347%	288
Remaining individualsnot grpmax-eligible	0.0465%	2,149
European (non-Finnish)	0.04%	2,502
South Asian	0.03%	3,339
Admixed American	0.0167%	5,975
East Asian	0.00447%	22,370
African / African-American	0.004%	25,001
Finnishnot grpmax-eligible	0.00158%	63,304

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.Ala9Val
Coding: c.26C>T
MANE Select: NM_145038
dbSNP: rs146049908
Type: single nucleotide variant
Location: chr2:26402015 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB

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-ala9val (accessed [today's date]).

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