Is RD3 p.Asp83Val (c.248A>T) pathogenic?

RD3 p.Asp83Val (c.248A>T) is classified Uncertain significance in RD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-04). AlphaMissense: likely benign (0.2656); Very rare (popmax 0.000124%); Associated with Inborn genetic diseases.

What condition is associated with RD3 p.Asp83Val (c.248A>T)?

RD3 p.Asp83Val (c.248A>T) is associated with Inborn genetic diseases (ClinVar).

How common is RD3 p.Asp83Val (c.248A>T) in the general population?

RD3 p.Asp83Val (c.248A>T) is very rare (popmax 0.000124%) (gnomAD).

What do computational predictors say about RD3 p.Asp83Val (c.248A>T)?

AlphaMissense predicts likely benign (score 0.2656) — an in-silico prediction, not a clinical call.

RD3 p.Asp83Val

c.248A>T · VCV4863097

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2656 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2656	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -11.98	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.12	GERP 0.99, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 2,376 bp · p 0.68 · regional, not allelic
Overall
CADD	19.97	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 0.000124%

Overall 0.000124% 2/1,614,264 alleles · very rare exomes 2/1,461,892 · genomes 0/152,372 · joint denominator

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: RD3
Protein: p.Asp83Val
Coding: c.248A>T
MANE Select: NM_001164688
Type: single nucleotide variant
Location: chr1:211481168 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 1 PDB
Residue 83: an α-helix

Full RD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RD3 p.Ala135Val Uncertain significance ★★ ⚠ same condition
RD3 p.Arg15Gln Uncertain significance ★★ ⚠ same condition
RD3 p.Arg15Trp Uncertain significance ★★ ⚠ same condition
RD3 p.Asp165Asn Uncertain significance ★★ ⚠ same condition
RD3 p.Asp176Gly Uncertain significance ★★ ⚠ same condition
RD3 p.Gly57Ser Uncertain significance ★★ ⚠ same condition
RD3 p.Ile169Val Uncertain significance ★★ ⚠ same condition
RD3 p.Leu7His Uncertain significance ★★ ⚠ same condition

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/rd3-p-asp83val (accessed [today's date]).

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