Is DALRD3 p.Pro129Arg (c.386C>G) pathogenic?

DALRD3 p.Pro129Arg (c.386C>G) is classified Uncertain significance in DALRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). AlphaMissense: likely benign (0.1382); Ultra-rare (popmax 0.0225%, mid).

How common is DALRD3 p.Pro129Arg (c.386C>G) in the general population?

DALRD3 p.Pro129Arg (c.386C>G) is ultra-rare (popmax 0.0225%, mid) (gnomAD).

What do computational predictors say about DALRD3 p.Pro129Arg (c.386C>G)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

DALRD3 p.Pro129Arg

c.386C>G · rs748420382 · VCV2523477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -9.75	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 5.7	GERP -0.058, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,973 bp · p 0.019 · regional, not allelic
Overall
CADD	17.45	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 0.0225% Middle Eastern · 1/4,444 alleles

Filtering AF 0.000644% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.00108% 16/1,485,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0225%	4,444
Admixed American	0.00243%	41,210
African / African-American	0.0014%	71,246
European (non-Finnish)	0.00115%	86,687

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.Pro129Arg
Coding: c.386C>G
MANE Select: NM_001009996
dbSNP: rs748420382
Type: single nucleotide variant
Location: chr3:49018098 (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.Pro129Leu Uncertain significance ★ ⚠ same residue
DALRD3 p.Pro129Ser 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

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-pro129arg (accessed [today's date]).

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