Is AHR p.Ser693Phe (c.2078C>T) pathogenic?

AHR p.Ser693Phe (c.2078C>T) is classified Uncertain significance in AHR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely benign (0.1153); Very rare (popmax 0.00167%, amr).

How common is AHR p.Ser693Phe (c.2078C>T) in the general population?

AHR p.Ser693Phe (c.2078C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AHR p.Ser693Phe (c.2078C>T)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

AHR p.Ser693Phe

c.2078C>T · rs1782400368 · VCV841046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.56	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 0.6	GERP 0.46
Regional constraint	o/e 1.12	unconstrained · MANE · 4,073 bp · p 0.0061 · regional, not allelic
Overall
CADD	14.08	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 0.00167% Admixed American · 1/60,008 alleles

Overall 0.000657% 1/152,208 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.Ser693Phe
Coding: c.2078C>T
MANE Select: NM_001621
dbSNP: rs1782400368
Type: single nucleotide variant
Location: chr7:17339903 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.88 · 3 PDB
Residue 693: a UniProt-annotated variant site (in fvh3; likely pathogenic; decreased protein abundance in homozygous patient cells; results in decreased ligand-activated transcription activator activity; cyp1a1 and cyp1b1 expression levels in homozygous patient cells treated with benzanthracene are reduced compared to controls)

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-ser693phe (accessed [today's date]).

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