Is DIRAS3 p.Thr69= (c.207C>T) pathogenic?

DIRAS3 p.Thr69= (c.207C>T) is classified Likely benign in DIRAS3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-16). Ultra-rare (popmax 0.0333%, afr); Associated with DIRAS3-related disorder.

What condition is associated with DIRAS3 p.Thr69= (c.207C>T)?

DIRAS3 p.Thr69= (c.207C>T) is associated with DIRAS3-related disorder (ClinVar).

How common is DIRAS3 p.Thr69= (c.207C>T) in the general population?

DIRAS3 p.Thr69= (c.207C>T) is ultra-rare (popmax 0.0333%, afr) (gnomAD).

DIRAS3 p.Thr69=

c.207C>T · rs554165010 · VCV3032282

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, afr)

Conditions

DIRAS3-related disorder

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 -1	GERP -4.7
Overall
CADD	1.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% African / African-American · 25/75,044 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00204% 33/1,614,200 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0333%	3,002
Admixed American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0064%	15,626

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: DIRAS3
Protein: p.Thr69=
Coding: c.207C>T
MANE Select: NM_004675
dbSNP: rs554165010
Type: single nucleotide variant
Location: chr1:68047091 (GRCh38)
Gene constraint: LOEUF 1.84 · pLI 0.34 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.19 · 1 PDB
Residue 69: a binding site

Full DIRAS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIRAS3-related disorder

Similar variants

DIRAS3 p.Ala129Thr Uncertain significance ★ ⚠ same type
DIRAS3 p.Arg18Gln Uncertain significance ★ ⚠ same type
DIRAS3 p.Arg18Trp Uncertain significance ★ ⚠ same type
DIRAS3 p.Arg27Gly Uncertain significance ★ ⚠ same type
DIRAS3 p.Arg99Leu Uncertain significance ★ ⚠ same type
DIRAS3 p.Asn174His Uncertain significance ★ ⚠ same type
DIRAS3 p.Asn217Ser Uncertain significance ★ ⚠ same type
DIRAS3 p.Gln102Arg 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/diras3-p-thr69 (accessed [today's date]).

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