Is CHRDL1 p.Ser210Cys (c.629C>G) pathogenic?

CHRDL1 p.Ser210Cys (c.629C>G) is classified Uncertain significance in CHRDL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.1983); Rare (popmax 0.201%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHRDL1 p.Ser210Cys (c.629C>G)?

CHRDL1 p.Ser210Cys (c.629C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHRDL1 p.Ser210Cys (c.629C>G) in the general population?

CHRDL1 p.Ser210Cys (c.629C>G) is rare (popmax 0.201%, amr) (gnomAD).

What do computational predictors say about CHRDL1 p.Ser210Cys (c.629C>G)?

AlphaMissense predicts likely benign (score 0.1983) — an in-silico prediction, not a clinical call.

CHRDL1 p.Ser210Cys

c.629C>G · VCV3492471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1983 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.201%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1983	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 116 kb · p 0.22 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S209C vs ClinVar S210C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.201% Admixed American · 91/45,190 alleles

Filtering AF 0.168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.156%

Overall 0.0476% 574/1,205,265 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.201%	497
Remaining individualsnot grpmax-eligible	0.0654%	1,529
European (non-Finnish)	0.0496%	2,015
South Asian	0.0107%	9,304
African / African-American	0.00526%	19,002

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: CHRDL1
Protein: p.Ser210Cys
Coding: c.629C>G
MANE Select: NM_001143981
Type: single nucleotide variant
Location: chrX:110694312 (GRCh38)
Structure: AlphaFold pLDDT 69.79
Residue 210: the 'disordered' region

Full CHRDL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRDL1 p.Glu423Asp Uncertain significance ★★ ⚠ same condition
CHRDL1 p.Gln197= Benign/Likely benign ★★ same condition
CHRDL1 c.542-8A>G Conflicting classifications of pathogenicity ★ same condition
CHRDL1 p.Ala229Val Uncertain significance ★ ⚠ same condition
CHRDL1 p.Arg196Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CHRDL1 p.Arg196Trp Uncertain significance ★ ⚠ same condition
CHRDL1 p.Arg201Lys Uncertain significance ★ ⚠ same condition
CHRDL1 p.Arg209Cys Uncertain significance ★ ⚠ same condition

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/chrdl1-p-ser210cys (accessed [today's date]).

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