Is DRC1 p.His426Arg (c.1277A>G) pathogenic?

DRC1 p.His426Arg (c.1277A>G) is classified Uncertain significance in DRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-05). AlphaMissense: likely benign (0.1574); Absent from gnomAD v4.1.

How common is DRC1 p.His426Arg (c.1277A>G) in the general population?

DRC1 p.His426Arg (c.1277A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRC1 p.His426Arg (c.1277A>G)?

AlphaMissense predicts likely benign (score 0.1574) — an in-silico prediction, not a clinical call.

DRC1 p.His426Arg

c.1277A>G · rs1558451805 · VCV2571772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1574 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1574	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -6.98	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 55 kb · p 0.71 · regional, not allelic
Overall
CADD	22.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRC1
Protein: p.His426Arg
Coding: c.1277A>G
MANE Select: NM_145038
dbSNP: rs1558451805
Type: single nucleotide variant
Location: chr2:26444829 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.44 · 1 PDB
Residue 426: 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

Similar variants

DRC1 p.Gln118Ter Pathogenic/Likely pathogenic ★★ same type
DRC1 p.Gln337Ter Pathogenic/Likely pathogenic ★★ same type
DRC1 p.Ser642Ter Pathogenic/Likely pathogenic ★★ same type
DRC1 p.Ala250Val Uncertain significance ★★ ⚠ same type
DRC1 p.Ala391Val Uncertain significance ★★ ⚠ same type
DRC1 p.Ala416Gly Uncertain significance ★★ ⚠ same type
DRC1 p.Ala45Val Uncertain significance ★★ ⚠ same type
DRC1 p.Ala473Val Uncertain significance ★★ ⚠ same type

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-his426arg (accessed [today's date]).

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