Is AHR p.Ser447Arg (c.1341C>G) pathogenic?

AHR p.Ser447Arg (c.1341C>G) is classified Uncertain significance in AHR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1263); Very rare (popmax 0.00534%, afr).

How common is AHR p.Ser447Arg (c.1341C>G) in the general population?

AHR p.Ser447Arg (c.1341C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about AHR p.Ser447Arg (c.1341C>G)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

AHR p.Ser447Arg

c.1341C>G · VCV4639403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.82	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 -0.68	GERP -3.8
Regional constraint	o/e 1.12	unconstrained · MANE · 4,073 bp · p 0.0061 · regional, not allelic
Overall
CADD	2.066	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 0.00534% African / African-American · 4/74,922 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,054 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: AHR
Protein: p.Ser447Arg
Coding: c.1341C>G
MANE Select: NM_001621
Type: single nucleotide variant
Location: chr7:17339166 (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.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
AHR p.Gln113His 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-ser447arg (accessed [today's date]).

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