Is CHRD p.Gly387Ser (c.1159G>A) pathogenic?

CHRD p.Gly387Ser (c.1159G>A) is classified Benign in CHRD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-29). AlphaMissense: likely benign (0.0752); Low-frequency (popmax 4.86%, afr).

How common is CHRD p.Gly387Ser (c.1159G>A) in the general population?

CHRD p.Gly387Ser (c.1159G>A) is low-frequency (popmax 4.86%, afr) (gnomAD).

What do computational predictors say about CHRD p.Gly387Ser (c.1159G>A)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

CHRD p.Gly387Ser

c.1159G>A · rs34147749 · VCV780902

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.86%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.64	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 2.6	GERP 1.2, phastCons 0.065
Regional constraint	o/e 0.92	unconstrained · MANE · 9,100 bp · p 0.0047 · regional, not allelic
Overall
CADD	17.45	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.86% African / African-American · 3,640/74,924 alleles

Filtering AF 4.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.67%

Overall 0.263% 4,238/1,611,056 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.86%	21
Admixed American	0.395%	253
Remaining individualsnot grpmax-eligible	0.353%	283
Middle Eastern	0.326%	307
South Asian	0.00992%	10,081
European (non-Finnish)	0.00967%	10,342

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.Gly387Ser
Coding: c.1159G>A
MANE Select: NM_003741
dbSNP: rs34147749
Type: single nucleotide variant
Location: chr3:184383109 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95 · 3 PDB
Residue 387: the chrd 2 domain

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

Similar variants

CHRD p.Gln608= 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
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-gly387ser (accessed [today's date]).

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