Is AHRR p.Pro438= (c.1314G>A) pathogenic?

AHRR p.Pro438= (c.1314G>A) is classified Likely benign in AHRR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Rare (popmax 0.187%, eas).

How common is AHRR p.Pro438= (c.1314G>A) in the general population?

AHRR p.Pro438= (c.1314G>A) is rare (popmax 0.187%, eas) (gnomAD).

AHRR p.Pro438=

c.1314G>A · rs370604768 · VCV2655247

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.187%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -2.8
Overall
CADD	0.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.187% East Asian · 84/44,846 alleles

Filtering AF 0.155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.043% 693/1,612,186 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.187%	534
Finnishnot grpmax-eligible	0.0983%	1,018
Remaining individualsnot grpmax-eligible	0.0705%	1,419
European (non-Finnish)	0.0415%	2,412
South Asian	0.0143%	6,992
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,516

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.Pro438=
Coding: c.1314G>A
MANE Select: NM_001377236
dbSNP: rs370604768
Type: single nucleotide variant
Location: chr5:434054 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.28 · 1 PDB

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

Similar variants

AHRR p.Pro438Leu Uncertain significance ★ ⚠ same residue
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

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-pro438 (accessed [today's date]).

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