Is DIXDC1 p.Arg265Ter (c.793C>T) pathogenic?

DIXDC1 p.Arg265Ter (c.793C>T) is classified Likely pathogenic in DIXDC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-12-01). Very rare (popmax 0.0022%, sas); Associated with obesity disorder.

What condition is associated with DIXDC1 p.Arg265Ter (c.793C>T)?

DIXDC1 p.Arg265Ter (c.793C>T) is associated with obesity disorder (ClinVar).

How common is DIXDC1 p.Arg265Ter (c.793C>T) in the general population?

DIXDC1 p.Arg265Ter (c.793C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

DIXDC1 p.Arg265Ter

c.793C>T · rs1419374563 · VCV631529

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

obesity disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.73, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,064 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000821% 12/1,461,592 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,532
Remaining individualsnot grpmax-eligible	0.0016%	62,482
Finnishnot grpmax-eligible	0.00156%	64,008
African / African-American	0.00133%	75,020
European (non-Finnish)	0.000593%	168,552

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: DIXDC1
Protein: p.Arg265Ter
Coding: c.793C>T
MANE Select: NM_001037954
dbSNP: rs1419374563
Type: single nucleotide variant
Location: chr11:111982362 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.52 · 1 PDB
Residue 265: the 'actin-binding' region

Full DIXDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

obesity disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIXDC1 p.Asn19Asp Benign ★★ same type
DIXDC1 p.Asp608= Benign ★★ same type
DIXDC1 p.Ala156Pro Uncertain significance ★ ⚠ same type
DIXDC1 p.Ala25Pro Uncertain significance ★ ⚠ same type
DIXDC1 p.Ala39Val Uncertain significance ★ ⚠ same type
DIXDC1 p.Arg138Gln Uncertain significance ★ ⚠ same type
DIXDC1 p.Arg199Gln Uncertain significance ★ ⚠ same type
DIXDC1 p.Arg199Trp 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/dixdc1-p-arg265ter (accessed [today's date]).

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