Is OPRD1 p.Pro103Thr (c.307C>A) pathogenic?

OPRD1 p.Pro103Thr (c.307C>A) is classified Uncertain significance in OPRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.959); Very rare (popmax 0.00203%, nfe).

How common is OPRD1 p.Pro103Thr (c.307C>A) in the general population?

OPRD1 p.Pro103Thr (c.307C>A) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about OPRD1 p.Pro103Thr (c.307C>A)?

AlphaMissense predicts likely pathogenic (score 0.959) — an in-silico prediction, not a clinical call.

OPRD1 p.Pro103Thr

c.307C>A · rs937990510 · VCV2385794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.959	likely pathogenic
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -10.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 51 kb · p 0.006 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00203% European (non-Finnish) · 24/1,180,054 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,614,066 alleles · very rare exomes 24/1,461,808 · genomes 1/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,169
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: OPRD1
Protein: p.Pro103Thr
Coding: c.307C>A
MANE Select: NM_000911
dbSNP: rs937990510
Type: single nucleotide variant
Location: chr1:28859033 (GRCh38)
Gene constraint: LOEUF 1.445 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.07 · 18 PDB
Residue 103: an α-helix

Full OPRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OPRD1 p.Ala195Thr Uncertain significance ★ ⚠ same type
OPRD1 p.Ala26Ser Uncertain significance ★ ⚠ same type
OPRD1 p.Ala275Thr Uncertain significance ★ ⚠ same type
OPRD1 p.Ala370Ser Uncertain significance ★ ⚠ same type
OPRD1 p.Ala61Val Uncertain significance ★ ⚠ same type
OPRD1 p.Ala9Thr Uncertain significance ★ ⚠ same type
OPRD1 p.Arg160Cys Uncertain significance ★ ⚠ same type
OPRD1 p.Arg190Cys 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/oprd1-p-pro103thr (accessed [today's date]).

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