Is ADPRH p.Trp191Ser (c.572G>C) pathogenic?

ADPRH p.Trp191Ser (c.572G>C) is classified Uncertain significance in ADPRH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely pathogenic (0.9361); Ultra-rare (popmax 0.0196%, nfe).

How common is ADPRH p.Trp191Ser (c.572G>C) in the general population?

ADPRH p.Trp191Ser (c.572G>C) is ultra-rare (popmax 0.0196%, nfe) (gnomAD).

What do computational predictors say about ADPRH p.Trp191Ser (c.572G>C)?

AlphaMissense predicts likely pathogenic (score 0.9361) — an in-silico prediction, not a clinical call.

ADPRH p.Trp191Ser

c.572G>C · VCV3501824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9361 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9361	likely pathogenic · top 7% in ADPRH
REVEL	0.507	indeterminate
SaProt	LLR -17.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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	32.0	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 0.0196% European (non-Finnish) · 231/1,179,996 alleles

Filtering AF 0.0175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.0146% 236/1,613,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0196%	5,108
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00267%	37,455

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.Trp191Ser
Coding: c.572G>C
MANE Select: NM_001125
Type: single nucleotide variant
Location: chr3:119586558 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.46 · 4 PDB
Residue 191: 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.Ala341Thr Uncertain significance ★ ⚠ same type
ADPRH p.Ala64Val Uncertain significance ★ ⚠ same type
ADPRH p.Ala70Gly 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-trp191ser (accessed [today's date]).

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