Is DRC4 p.Ile59Phe (c.175A>T) pathogenic?

DRC4 p.Ile59Phe (c.175A>T) is classified Uncertain significance in DRC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.5965); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DRC4 p.Ile59Phe (c.175A>T)?

DRC4 p.Ile59Phe (c.175A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DRC4 p.Ile59Phe (c.175A>T) in the general population?

DRC4 p.Ile59Phe (c.175A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRC4 p.Ile59Phe (c.175A>T)?

AlphaMissense predicts likely pathogenic (score 0.5965) — an in-silico prediction, not a clinical call.

DRC4 p.Ile59Phe

c.175A>T · rs2036556362 · VCV3098684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5965	likely pathogenic
REVEL	0.439	indeterminate
SaProt	LLR -11.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DRC4
Protein: p.Ile59Phe
Coding: c.175A>T
MANE Select: NM_001481
dbSNP: rs2036556362
Type: single nucleotide variant
Location: chr16:90031383 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 59: the 'regulates microtubule-binding' region

Full DRC4 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

DRC4 p.Ala280Thr Uncertain significance ★★ ⚠ same condition
DRC4 p.Ala460Pro Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg203Gln Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg278Cys Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg342Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg369Cys Uncertain significance ★★ ⚠ same condition
DRC4 p.Asp239Tyr Uncertain significance ★★ ⚠ same condition
DRC4 p.Glu344Lys 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/drc4-p-ile59phe (accessed [today's date]).

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