Is DRC5 p.Ile423Phe (c.1267A>T) pathogenic?

DRC5 p.Ile423Phe (c.1267A>T) is classified Uncertain significance in DRC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.2872); Absent from gnomAD v4.1.

How common is DRC5 p.Ile423Phe (c.1267A>T) in the general population?

DRC5 p.Ile423Phe (c.1267A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRC5 p.Ile423Phe (c.1267A>T)?

AlphaMissense predicts likely benign (score 0.2872) — an in-silico prediction, not a clinical call.

DRC5 p.Ile423Phe

c.1267A>T · rs200571497 · VCV3175370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2872	likely benign
REVEL	0.321	indeterminate
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.88, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,641 bp · p 0.39 · regional, not allelic
Overall
CADD	21.0	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: DRC5
Protein: p.Ile423Phe
Coding: c.1267A>T
MANE Select: NM_182539
dbSNP: rs200571497
Type: single nucleotide variant
Location: chr6:44282139 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 1 PDB

Full DRC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC5 p.Ala351Asp Uncertain significance ★ ⚠ same type
DRC5 p.Ala381Thr Uncertain significance ★ ⚠ same type
DRC5 p.Ala385Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg133His Uncertain significance ★ ⚠ same type
DRC5 p.Arg133Pro Uncertain significance ★ ⚠ same type
DRC5 p.Arg158Gln Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Trp 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/drc5-p-ile423phe (accessed [today's date]).

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