Is DRC1 p.Ala391Val (c.1172C>T) pathogenic?

DRC1 p.Ala391Val (c.1172C>T) is classified Uncertain significance in DRC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-17). AlphaMissense: likely benign (0.1337); Ultra-rare (popmax 0.0667%, amr); Associated with Inborn genetic diseases.

What condition is associated with DRC1 p.Ala391Val (c.1172C>T)?

DRC1 p.Ala391Val (c.1172C>T) is associated with Inborn genetic diseases, primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Ala391Val (c.1172C>T) in the general population?

DRC1 p.Ala391Val (c.1172C>T) is ultra-rare (popmax 0.0667%, amr) (gnomAD).

What do computational predictors say about DRC1 p.Ala391Val (c.1172C>T)?

AlphaMissense predicts likely benign (score 0.1337) — an in-silico prediction, not a clinical call.

DRC1 p.Ala391Val

c.1172C>T · rs148372110 · VCV454977

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1337 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1337	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.46	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 2.1	GERP -0.73, phastCons 0.02
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	18.27	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 0.0667% Admixed American · 40/59,994 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.0379% 612/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0667%	1,500
European (non-Finnish)	0.0462%	2,165
Remaining individualsnot grpmax-eligible	0.0272%	3,675
African / African-American	0.0133%	7,491

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.Ala391Val
Coding: c.1172C>T
MANE Select: NM_145038
dbSNP: rs148372110
Type: single nucleotide variant
Location: chr2:26444724 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 391: 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.Ala416Gly Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala45Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala473Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala475Val 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-ala391val (accessed [today's date]).

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