Is CHD1 p.Pro91Ser (c.271C>T) pathogenic?

CHD1 p.Pro91Ser (c.271C>T) is classified Uncertain significance in CHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-19). AlphaMissense: likely benign (0.2132); Ultra-rare (popmax 0.01%, sas); Associated with Pilarowski-Bjornsson syndrome.

What condition is associated with CHD1 p.Pro91Ser (c.271C>T)?

CHD1 p.Pro91Ser (c.271C>T) is associated with Pilarowski-Bjornsson syndrome (ClinVar).

How common is CHD1 p.Pro91Ser (c.271C>T) in the general population?

CHD1 p.Pro91Ser (c.271C>T) is ultra-rare (popmax 0.01%, sas) (gnomAD).

What do computational predictors say about CHD1 p.Pro91Ser (c.271C>T)?

AlphaMissense predicts likely benign (score 0.2132) — an in-silico prediction, not a clinical call.

CHD1 p.Pro91Ser

c.271C>T · rs747828889 · VCV1031943

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2132 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Pilarowski-Bjornsson syndrome

Computational evidence

Protein change
AlphaMissense	0.2132	likely benign
REVEL	0.58	indeterminate
SaProt	LLR -4.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.65 · regional, not allelic
Overall
CADD	26.4	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 0.01% South Asian · 9/90,000 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0039%

Overall 0.000625% 10/1,600,962 alleles · ultra-rare exomes 10/1,448,900 · genomes 0/152,062 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.00161%	61,950

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: CHD1
Protein: p.Pro91Ser
Coding: c.271C>T
MANE Select: NM_001270
dbSNP: rs747828889
Type: single nucleotide variant
Location: chr5:98903893 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 91: 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.Tyr1598His 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-pro91ser (accessed [today's date]).

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