Is DIXDC1 p.Arg47Gln (c.140G>A) pathogenic?

DIXDC1 p.Arg47Gln (c.140G>A) is classified Uncertain significance in DIXDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.1441); Very rare (popmax 0.00133%, afr).

How common is DIXDC1 p.Arg47Gln (c.140G>A) in the general population?

DIXDC1 p.Arg47Gln (c.140G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DIXDC1 p.Arg47Gln (c.140G>A)?

AlphaMissense predicts likely benign (score 0.1441) — an in-silico prediction, not a clinical call.

DIXDC1 p.Arg47Gln

c.140G>A · VCV3840227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1441	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -3.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 31 kb · p 0.21 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.00133% African / African-American · 1/75,012 alleles

Overall 0.000205% 3/1,459,980 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,012
South Asian	0.0011%	90,504
European (non-Finnish)	8.48e-05%	1,179,312

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.Arg47Gln
Coding: c.140G>A
MANE Select: NM_001037954
Type: single nucleotide variant
Location: chr11:111964628 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.52 · 1 PDB
Residue 47: the calponin-homology (ch) domain

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

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-arg47gln (accessed [today's date]).

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