Is AHR p.Pro428Ser (c.1282C>T) pathogenic?

AHR p.Pro428Ser (c.1282C>T) is classified Uncertain significance in AHR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-29). AlphaMissense: likely benign (0.1051); Ultra-rare (popmax 0.0133%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with AHR p.Pro428Ser (c.1282C>T)?

AHR p.Pro428Ser (c.1282C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is AHR p.Pro428Ser (c.1282C>T) in the general population?

AHR p.Pro428Ser (c.1282C>T) is ultra-rare (popmax 0.0133%, nfe) (gnomAD).

What do computational predictors say about AHR p.Pro428Ser (c.1282C>T)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

AHR p.Pro428Ser

c.1282C>T · rs750208257 · VCV1523275

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.93	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 1.1	GERP 0.95, phastCons 0.001
Regional constraint	o/e 1.12	unconstrained · MANE · 4,073 bp · p 0.0061 · regional, not allelic
Overall
CADD	17.48	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 0.0133% European (non-Finnish) · 157/1,180,024 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0104% 168/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0133%	7,516
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.00329%	30,359
Finnishnot grpmax-eligible	0.00312%	32,008
African / African-American	0.00267%	37,507

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: AHR
Protein: p.Pro428Ser
Coding: c.1282C>T
MANE Select: NM_001621
dbSNP: rs750208257
Type: single nucleotide variant
Location: chr7:17339107 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.88 · 3 PDB

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AHR p.Pro428Gln Uncertain significance ★ ⚠ same residue
AHR p.Met650Val Uncertain significance ★★ ⚠ same condition
AHR p.Ser567Cys Uncertain significance ★ ⚠ same condition
AHR p.Ile575Ser Uncertain significance ⚠ same condition
AHR p.Leu469Phe Uncertain significance ⚠ same condition
AHR p.Ala313Thr Uncertain significance ★★ ⚠ same type
AHR p.Ala459Ser Uncertain significance ★★ ⚠ same type
AHR p.Arg352Trp 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/ahr-p-pro428ser (accessed [today's date]).

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