Is AHRR p.Ser30Pro (c.88T>C) pathogenic?

AHRR p.Ser30Pro (c.88T>C) is classified Uncertain significance in AHRR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.5673); Ultra-rare (popmax 0.0276%, nfe).

How common is AHRR p.Ser30Pro (c.88T>C) in the general population?

AHRR p.Ser30Pro (c.88T>C) is ultra-rare (popmax 0.0276%, nfe) (gnomAD).

What do computational predictors say about AHRR p.Ser30Pro (c.88T>C)?

AlphaMissense predicts likely pathogenic (score 0.5673) — an in-silico prediction, not a clinical call.

AHRR p.Ser30Pro

c.88T>C · rs201437247 · VCV3102155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5673 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5673	likely pathogenic
REVEL	0.185	benign-leaning
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 91 kb · p 0.24 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S34P vs ClinVar S30P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0276% European (non-Finnish) · 326/1,179,714 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.022% 355/1,612,130 alleles · ultra-rare exomes 339/1,459,964 · genomes 16/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0276%	3,619
Remaining individualsnot grpmax-eligible	0.0192%	5,204
Finnishnot grpmax-eligible	0.0175%	5,704
Admixed American	0.005%	19,985
African / African-American	0.004%	24,989

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: AHRR
Protein: p.Ser30Pro
Coding: c.88T>C
MANE Select: NM_001377236
dbSNP: rs201437247
Type: single nucleotide variant
Location: chr5:353755 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.28 · 1 PDB
Residue 34 UniProt numbering: the bhlh domain; the 'disordered' region; the 'basic motif' region

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

Similar variants

AHRR p.Arg453Cys Benign ★★ same type
AHRR c.709-131C>G Uncertain significance ★ same type
AHRR c.709-143C>T Uncertain significance ★ same type
AHRR c.709-147G>T Uncertain significance ★ same type
AHRR c.709-166G>A Uncertain significance ★ same type
AHRR c.709-167C>T Uncertain significance ★ same type
AHRR p.Ala194Val Uncertain significance ★ ⚠ same type
AHRR p.Ala24Thr 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/ahrr-p-ser30pro (accessed [today's date]).

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