Is CRHR2 p.Ala32= (c.96C>T) pathogenic?

CRHR2 p.Ala32= (c.96C>T) is classified Benign in CRHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-21). Common (popmax 12.6%, afr) — too common for a highly-penetrant pathogenic allele.

CRHR2 p.Ala32=

Q: How common is CRHR2 p.Ala32= (c.96C>T) in the general population?

CRHR2 p.Ala32= (c.96C>T) is common (popmax 12.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.96C>T · rs61749076 · VCV778299

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 12.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.6	GERP -2.7
Overall
CADD	2.697	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.6% African / African-American · 9,221/73,114 alleles

Filtering AF 12.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.3%

Overall 0.729% 11,303/1,550,134 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.6%	8
Middle Eastern	1.65%	60
Remaining individualsnot grpmax-eligible	1.06%	94
Admixed American	0.914%	109
Finnishnot grpmax-eligible	0.0801%	1,248
European (non-Finnish)	0.0683%	1,465
South Asian	0.05%	2,001
Ashkenazi Jewishnot grpmax-eligible	0.0244%	4,092

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: CRHR2
Protein: p.Ala32=
Coding: c.96C>T
MANE Select: NM_001883 · reported on NM_001202475
dbSNP: rs61749076
Type: single nucleotide variant
Location: chr7:30689279 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.80 · 6 PDB
Residue 32: a disulfide bond

Full CRHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRHR2 p.Arg114Cys Uncertain significance ★ ⚠ same type
CRHR2 p.Arg142Trp Uncertain significance ★ same type
CRHR2 p.Arg145Cys Uncertain significance ★ same type
CRHR2 p.Arg145Leu Uncertain significance ★ ⚠ same type
CRHR2 p.Arg148Trp Uncertain significance ★ ⚠ same type
CRHR2 p.Arg221Cys Uncertain significance ★ ⚠ same type
CRHR2 p.Arg221His Uncertain significance ★ ⚠ same type
CRHR2 p.Arg223His 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/crhr2-p-ala32 (accessed [today's date]).

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