Is DRC1 p.Arg554Gln (c.1661G>A) pathogenic?

DRC1 p.Arg554Gln (c.1661G>A) is classified Likely benign in DRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.0818); Very rare (popmax 0.00544%, afr); Associated with Inborn genetic diseases.

What condition is associated with DRC1 p.Arg554Gln (c.1661G>A)?

DRC1 p.Arg554Gln (c.1661G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DRC1 p.Arg554Gln (c.1661G>A) in the general population?

DRC1 p.Arg554Gln (c.1661G>A) is very rare (popmax 0.00544%, afr) (gnomAD).

What do computational predictors say about DRC1 p.Arg554Gln (c.1661G>A)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

DRC1 p.Arg554Gln

c.1661G>A · rs374438636 · VCV3085723

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00544%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.48	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 -0.23	GERP -3.1
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	8.43	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 0.00544% African / African-American · 4/73,488 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000933% 15/1,607,514 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00544%	18,372
South Asian	0.00331%	30,178
East Asian	0.00224%	44,626
Remaining individualsnot grpmax-eligible	0.00161%	62,284
European (non-Finnish)	0.00051%	196,212

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.Arg554Gln
Coding: c.1661G>A
MANE Select: NM_145038
dbSNP: rs374438636
Type: single nucleotide variant
Location: chr2:26450653 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 554: 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 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

Similar variants

DRC1 p.Arg554Ter Pathogenic ★ same residue
DRC1 p.Ala250Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala391Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala45Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Ala473Val Uncertain significance ★★ ⚠ same condition
DRC1 p.Arg206Gln Uncertain significance ★★ ⚠ same condition
DRC1 p.Arg46Leu Uncertain significance ★★ ⚠ same condition
DRC1 p.Arg736Gln 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-arg554gln (accessed [today's date]).

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