Is DRC1 p.Arg736Gln (c.2207G>A) pathogenic?

DRC1 p.Arg736Gln (c.2207G>A) is classified Uncertain significance in DRC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0802); Very rare (popmax 0.00593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DRC1 p.Arg736Gln (c.2207G>A)?

DRC1 p.Arg736Gln (c.2207G>A) is associated with Inborn genetic diseases, primary ciliary dyskinesia (ClinVar).

How common is DRC1 p.Arg736Gln (c.2207G>A) in the general population?

DRC1 p.Arg736Gln (c.2207G>A) is very rare (popmax 0.00593%, nfe) (gnomAD).

What do computational predictors say about DRC1 p.Arg736Gln (c.2207G>A)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

DRC1 p.Arg736Gln

c.2207G>A · rs761603781 · VCV454987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.67	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.6	GERP -2.6
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	4.155	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 0.00593% European (non-Finnish) · 70/1,179,994 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00471% 76/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,857
Admixed American	0.00333%	29,990
Remaining individualsnot grpmax-eligible	0.0032%	31,242
East Asian	0.00223%	44,894
Finnishnot grpmax-eligible	0.00156%	64,036

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.Arg736Gln
Coding: c.2207G>A
MANE Select: NM_145038
dbSNP: rs761603781
Type: single nucleotide variant
Location: chr2:26456501 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 736: a UniProt-annotated variant site (in cild21; multiple flagellar abnormalities are present in patient sperm); a UniProt-annotated variant site (in spgf80; no protein detected in a homozygous patient sperm); a UniProt-annotated variant site (in cild21); a UniProt-annotated variant site (in spgf80)

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.Arg736Trp Uncertain significance ★ ⚠ same residue
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

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-arg736gln (accessed [today's date]).

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