Is ADPRH p.Ala341Thr (c.1021G>A) pathogenic?

ADPRH p.Ala341Thr (c.1021G>A) is classified Uncertain significance in ADPRH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.606); Very rare (popmax 0.000424%, nfe).

How common is ADPRH p.Ala341Thr (c.1021G>A) in the general population?

ADPRH p.Ala341Thr (c.1021G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ADPRH p.Ala341Thr (c.1021G>A)?

AlphaMissense predicts likely pathogenic (score 0.606) — an in-silico prediction, not a clinical call.

ADPRH p.Ala341Thr

c.1021G>A · VCV4638587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.606	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	LLR -13.64	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,705 bp · p 0.22 · regional, not allelic
Overall
CADD	24.9	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 0.000424% European (non-Finnish) · 5/1,179,750 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,196 alleles · very rare

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: ADPRH
Protein: p.Ala341Thr
Coding: c.1021G>A
MANE Select: NM_001125
Type: single nucleotide variant
Location: chr3:119587825 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.46 · 4 PDB
Residue 341: an α-helix

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

Similar variants

ADPRH p.Ala13Gly Uncertain significance ★ ⚠ same type
ADPRH p.Ala182Thr Uncertain significance ★ ⚠ same type
ADPRH p.Ala293Thr Uncertain significance ★ ⚠ same type
ADPRH p.Ala296Thr Uncertain significance ★ ⚠ same type
ADPRH p.Ala310Ser Uncertain significance ★ ⚠ same type
ADPRH p.Ala64Val Uncertain significance ★ ⚠ same type
ADPRH p.Ala70Gly Uncertain significance ★ ⚠ same type
ADPRH p.Arg160Gln 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/adprh-p-ala341thr (accessed [today's date]).

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