Is DALRD3 p.His348Arg (c.1043A>G) pathogenic?

DALRD3 p.His348Arg (c.1043A>G) is classified Uncertain significance in DALRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.0789); Ultra-rare (popmax 0.0336%, mid).

How common is DALRD3 p.His348Arg (c.1043A>G) in the general population?

DALRD3 p.His348Arg (c.1043A>G) is ultra-rare (popmax 0.0336%, mid) (gnomAD).

What do computational predictors say about DALRD3 p.His348Arg (c.1043A>G)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

DALRD3 p.His348Arg

c.1043A>G · VCV3499638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0336%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.27	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.15	GERP -1.7, phastCons 0.021
Regional constraint	o/e 1.09	unconstrained · MANE · 2,973 bp · p 0.019 · regional, not allelic
Overall
CADD	11.23	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0336% Middle Eastern · 2/5,950 alleles

Filtering AF 0.00592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00063% 10/1,587,248 alleles · ultra-rare exomes 9/1,435,062 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0336%	2,975
South Asian	0.00231%	43,335
Admixed American	0.00173%	57,766
Remaining individualsnot grpmax-eligible	0.00163%	61,240
European (non-Finnish)	0.000343%	291,352

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: DALRD3
Protein: p.His348Arg
Coding: c.1043A>G
MANE Select: NM_001009996
Type: single nucleotide variant
Location: chr3:49016632 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57

Full DALRD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DALRD3 p.His348Tyr Uncertain significance ★ ⚠ same residue
DALRD3 c.1512+18T>C Benign ★★ same type
DALRD3 p.Gln299Arg Benign ★★ same type
DALRD3 p.Gln299Ter Likely pathogenic ★ same type
DALRD3 c.1329+1G>A Uncertain significance ★ same type
DALRD3 c.-5T>C Uncertain significance ★ same type
DALRD3 p.Ala109Ser Uncertain significance ★ ⚠ same type
DALRD3 p.Ala149Ser 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/dalrd3-p-his348arg (accessed [today's date]).

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