Is CHD7 p.Phe2124Ser (c.6371T>C) pathogenic?

CHD7 p.Phe2124Ser (c.6371T>C) is classified Likely pathogenic in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-11). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Phe2124Ser (c.6371T>C)?

CHD7 p.Phe2124Ser (c.6371T>C) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Phe2124Ser (c.6371T>C) in the general population?

CHD7 p.Phe2124Ser (c.6371T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD7 p.Phe2124Ser (c.6371T>C)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

CHD7 p.Phe2124Ser

c.6371T>C · rs2488042663 · VCV2500730

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 2% in CHD7
REVEL	0.946	strongly pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 17 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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.Phe2124Ser
Coding: c.6371T>C
MANE Select: NM_017780
dbSNP: rs2488042663
Type: single nucleotide variant
Location: chr8:60853096 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

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

Similar variants

CHD7 p.Phe2124del Pathogenic/Likely pathogenic ★★ same residue
CHD7 p.Phe2124Cys Likely pathogenic ★ same residue
CHD7 p.Phe2124Leu Uncertain significance ★ ⚠ same residue
CHD7 c.2097-2A>G Pathogenic ★★ same condition
CHD7 c.2238+1G>A Pathogenic ★★ same condition
CHD7 c.2377-1G>A Likely pathogenic ★★ same condition
CHD7 c.2613+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.2836-1G>A Pathogenic/Likely 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-phe2124ser (accessed [today's date]).

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