Is CHD7 p.Ser2857Phe (c.8570C>T) pathogenic?

CHD7 p.Ser2857Phe (c.8570C>T) is classified Uncertain significance in CHD7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-12). AlphaMissense: likely benign (0.1519); Absent from gnomAD v4.1; Associated with CHD7-related disorder.

What condition is associated with CHD7 p.Ser2857Phe (c.8570C>T)?

CHD7 p.Ser2857Phe (c.8570C>T) is associated with CHD7-related disorder (ClinVar).

How common is CHD7 p.Ser2857Phe (c.8570C>T) in the general population?

CHD7 p.Ser2857Phe (c.8570C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD7 p.Ser2857Phe (c.8570C>T)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

CHD7 p.Ser2857Phe

c.8570C>T · VCV3346713

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

CHD7-related disorder

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.89, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 870 bp · p 0.43 · regional, not allelic
Overall
CADD	22.3	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 is an independent agreement signal.

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: CHD7
Protein: p.Ser2857Phe
Coding: c.8570C>T
MANE Select: NM_017780
Type: single nucleotide variant
Location: chr8:60865509 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2857: the 'disordered' region; a UniProt-annotated variant site (sequence variant)

Full CHD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHD7-related disorder

Similar variants

CHD7 p.Ser2857Ala Uncertain significance ★ ⚠ same residue
CHD7 p.Ser2857= Benign ★ same residue
CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.2958-3A>G Likely pathogenic ★★ same condition
CHD7 c.4185+1G>A Pathogenic ★★ same condition
CHD7 c.5210+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.5211-2A>G Pathogenic ★★ same condition
CHD7 p.Arg1219Ter Pathogenic ★★ 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/chd7-p-ser2857phe (accessed [today's date]).

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