Is CHD7 p.Ser708= (c.2124T>C) pathogenic?

CHD7 p.Ser708= (c.2124T>C) is classified Benign/Likely benign in CHD7 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-03). Common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Ser708= (c.2124T>C)?

CHD7 p.Ser708= (c.2124T>C) is associated with Inborn genetic diseases, CHARGE syndrome, hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

CHD7 p.Ser708=

Q: How common is CHD7 p.Ser708= (c.2124T>C) in the general population?

CHD7 p.Ser708= (c.2124T>C) is common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2124T>C · rs79302359 · VCV95777

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.74, phastCons 1
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.54% African / African-American · 4,158/74,998 alleles

Filtering AF 5.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.35%

Overall 0.77% 12,419/1,613,616 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.54%	18
South Asian	4.95%	20
Middle Eastern	4.05%	25
Ashkenazi Jewishnot grpmax-eligible	1.53%	65
Remaining individualsnot grpmax-eligible	1.11%	90
Admixed American	0.522%	192
European (non-Finnish)	0.173%	578
East Asian	0.0111%	8,972
Finnishnot grpmax-eligible	0.00781%	12,798

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: CHD7
Protein: p.Ser708=
Coding: c.2124T>C
MANE Select: NM_017780
dbSNP: rs79302359
Type: single nucleotide variant
Location: chr8:60795013 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 708: the 'disordered' region

Full CHD7 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

Also linked: CHARGE syndrome hypogonadotropic hypogonadism 5 with or without anosmia

Similar variants

CHD7 p.Ser708Asn Likely benign ★★ 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
CHD7 c.2836-2A>T Pathogenic ★★ same condition
CHD7 c.2957+2T>C 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-ser708 (accessed [today's date]).

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