Is DRC1 p.His28Arg (c.83A>G) pathogenic?

DRC1 p.His28Arg (c.83A>G) is classified Uncertain significance in DRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0847); Ultra-rare (popmax 0.0165%, sas); Associated with Inborn genetic diseases.

What condition is associated with DRC1 p.His28Arg (c.83A>G)?

DRC1 p.His28Arg (c.83A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DRC1 p.His28Arg (c.83A>G) in the general population?

DRC1 p.His28Arg (c.83A>G) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about DRC1 p.His28Arg (c.83A>G)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

DRC1 p.His28Arg

c.83A>G · rs771532771 · VCV3085729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -9.06	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 5.1	GERP 1.3, phastCons 0.35
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	13.37	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 0.0165% South Asian · 15/91,058 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00105% 17/1,612,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,071
European (non-Finnish)	0.00017%	589,897

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.His28Arg
Coding: c.83A>G
MANE Select: NM_145038
dbSNP: rs771532771
Type: single nucleotide variant
Location: chr2:26402072 (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

Similar variants

DRC1 p.His28Pro Uncertain significance ★ ⚠ 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-his28arg (accessed [today's date]).

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