Is DIRAS1 p.His66= (c.198C>T) pathogenic?

DIRAS1 p.His66= (c.198C>T) is classified Likely benign in DIRAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). Absent from gnomAD v4.1.

How common is DIRAS1 p.His66= (c.198C>T) in the general population?

DIRAS1 p.His66= (c.198C>T) is absent from gnomAD v4.1 (gnomAD).

DIRAS1 p.His66=

c.198C>T · VCV3272127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 2.6, phastCons 1
Overall
CADD	11.47	PHRED · no single calibrated threshold — expert panels disagree

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: DIRAS1
Protein: p.His66=
Coding: c.198C>T
MANE Select: NM_145173
Type: single nucleotide variant
Location: chr19:2717609 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 87.01 · 1 PDB
Residue 66: an α-helix

Full DIRAS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIRAS1 p.Ala145Ser Uncertain significance ★ ⚠ same type
DIRAS1 p.Arg181Gly Uncertain significance ★ ⚠ same type
DIRAS1 p.Arg190Gly Uncertain significance ★ ⚠ same type
DIRAS1 p.Arg190His Uncertain significance ★ ⚠ same type
DIRAS1 p.Asp113Asn Uncertain significance ★ ⚠ same type
DIRAS1 p.Asp178Glu Uncertain significance ★ ⚠ same type
DIRAS1 p.Glu41Lys Uncertain significance ★ ⚠ same type
DIRAS1 p.Gly109Ala 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/diras1-p-his66 (accessed [today's date]).

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