Is AHR p.Pro419Ser (c.1255C>T) pathogenic?

AHR p.Pro419Ser (c.1255C>T) is classified Uncertain significance in AHR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-06). AlphaMissense: likely benign (0.0872); Absent from gnomAD v4.1.

How common is AHR p.Pro419Ser (c.1255C>T) in the general population?

AHR p.Pro419Ser (c.1255C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AHR p.Pro419Ser (c.1255C>T)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

AHR p.Pro419Ser

c.1255C>T · rs775106689 · VCV2107280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.99	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 1.1, phastCons 0.044
Regional constraint	o/e 1.12	unconstrained · MANE · 4,073 bp · p 0.0061 · regional, not allelic
Overall
CADD	14.64	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AHR
Protein: p.Pro419Ser
Coding: c.1255C>T
MANE Select: NM_001621
dbSNP: rs775106689
Type: single nucleotide variant
Location: chr7:17339080 (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

Similar variants

AHR p.Pro419Thr Uncertain significance ★ ⚠ same residue
AHR p.Ala313Thr Uncertain significance ★★ ⚠ same type
AHR p.Ala459Ser Uncertain significance ★★ ⚠ same type
AHR p.Arg352Trp Uncertain significance ★★ ⚠ same type
AHR p.Asn179His Uncertain significance ★★ ⚠ same type
AHR p.Asn238Ser Uncertain significance ★★ ⚠ same type
AHR p.Asn789Ser Uncertain significance ★★ ⚠ same type
AHR p.Asp841Asn 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-pro419ser (accessed [today's date]).

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