Is CHD1 p.Ser69Pro (c.205T>C) pathogenic?

CHD1 p.Ser69Pro (c.205T>C) is classified Uncertain significance in CHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-10). AlphaMissense: likely benign (0.0797); Absent from gnomAD v4.1; Associated with Pilarowski-Bjornsson syndrome.

What condition is associated with CHD1 p.Ser69Pro (c.205T>C)?

CHD1 p.Ser69Pro (c.205T>C) is associated with Pilarowski-Bjornsson syndrome (ClinVar).

How common is CHD1 p.Ser69Pro (c.205T>C) in the general population?

CHD1 p.Ser69Pro (c.205T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD1 p.Ser69Pro (c.205T>C)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

CHD1 p.Ser69Pro

c.205T>C · rs753500340 · VCV1027854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Pilarowski-Bjornsson syndrome

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.505	indeterminate
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.65 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD1
Protein: p.Ser69Pro
Coding: c.205T>C
MANE Select: NM_001270
dbSNP: rs753500340
Type: single nucleotide variant
Location: chr5:98904947 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 69: the 'disordered' region

Full CHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Pilarowski-Bjornsson syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD1 p.Arg1659Thr Uncertain significance ★★ ⚠ same condition
CHD1 p.Arg1708Gln Uncertain significance ★★ same condition
CHD1 p.Arg233His Uncertain significance ★★ same condition
CHD1 p.Asn1518His Uncertain significance ★★ ⚠ same condition
CHD1 p.Asn557Lys Uncertain significance ★★ ⚠ same condition
CHD1 p.Asp221Val Uncertain significance ★★ ⚠ same condition
CHD1 p.Gly1113Arg Uncertain significance ★★ ⚠ same condition
CHD1 p.Pro91Ser 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/chd1-p-ser69pro (accessed [today's date]).

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