Is CHRD p.Pro772= (c.2316A>G) pathogenic?

CHRD p.Pro772= (c.2316A>G) is classified Benign in CHRD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-26). Common (popmax 6.47%, amr) — too common for a highly-penetrant pathogenic allele.

CHRD p.Pro772=

Q: How common is CHRD p.Pro772= (c.2316A>G) in the general population?

CHRD p.Pro772= (c.2316A>G) is common (popmax 6.47%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2316A>G · rs145052186 · VCV771358

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.47%, amr) — 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 -4.3	GERP -2.8
Overall
CADD	0.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.47% Admixed American · 3,885/60,010 alleles

Filtering AF 6.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.23%

Overall 0.294% 4,741/1,614,058 alleles · common exomes 3,888/1,461,870 · genomes 853/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	6.47%	15
East Asian	0.339%	295
African / African-American	0.336%	298
Remaining individualsnot grpmax-eligible	0.248%	403
Ashkenazi Jewishnot grpmax-eligible	0.203%	493
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.0195%	5,130
South Asian	0.00549%	18,214

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: CHRD
Protein: p.Pro772=
Coding: c.2316A>G
MANE Select: NM_003741
dbSNP: rs145052186
Type: single nucleotide variant
Location: chr3:184387076 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95 · 3 PDB

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

Similar variants

CHRD p.Gln608= Benign ★★ same type
CHRD p.Gly387Ser Benign ★★ same type
CHRD p.Thr301= Benign ★★ same type
CHRD p.Thr457Ser Likely benign ★★ same type
CHRD p.Ala251Glu Uncertain significance ★ ⚠ same type
CHRD p.Ala251Thr Uncertain significance ★ ⚠ same type
CHRD p.Ala27Pro Uncertain significance ★ ⚠ same type
CHRD p.Ala386Gly 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/chrd-p-pro772 (accessed [today's date]).

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