Is CHRD p.Arg596Gln (c.1787G>A) pathogenic?

CHRD p.Arg596Gln (c.1787G>A) is classified Uncertain significance in CHRD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.0653); Rare (popmax 0.588%, afr).

How common is CHRD p.Arg596Gln (c.1787G>A) in the general population?

CHRD p.Arg596Gln (c.1787G>A) is rare (popmax 0.588%, afr) (gnomAD).

What do computational predictors say about CHRD p.Arg596Gln (c.1787G>A)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

CHRD p.Arg596Gln

c.1787G>A · VCV4653528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.588%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.05	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 4.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 9,100 bp · p 0.0047 · regional, not allelic
Overall
CADD	21.1	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 0.588% African / African-American · 441/75,052 alleles

Filtering AF 0.542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.524%

Overall 0.0371% 598/1,613,954 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.588%	170
Remaining individualsnot grpmax-eligible	0.064%	1,563
Admixed American	0.0533%	1,876
Middle Eastern	0.0495%	2,021
South Asian	0.00769%	13,011
European (non-Finnish)	0.00619%	16,164
East Asian	0.00446%	22,440

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.Arg596Gln
Coding: c.1787G>A
MANE Select: NM_003741
Type: single nucleotide variant
Location: chr3:184385207 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95 · 3 PDB
Residue 596: the chrd 4 domain

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

Similar variants

CHRD p.Arg596Trp Uncertain significance ★ ⚠ same residue
CHRD p.Gln608= Benign ★★ same type
CHRD p.Gly387Ser Benign ★★ same type
CHRD p.Pro772= 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

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-arg596gln (accessed [today's date]).

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