Is CHD7 p.Arg1069Ter (c.3205C>T) pathogenic?

CHD7 p.Arg1069Ter (c.3205C>T) is classified Pathogenic in CHD7 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-12-30). Absent from gnomAD v4.1; Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.Arg1069Ter (c.3205C>T)?

CHD7 p.Arg1069Ter (c.3205C>T) is associated with hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome (ClinVar).

How common is CHD7 p.Arg1069Ter (c.3205C>T) in the general population?

CHD7 p.Arg1069Ter (c.3205C>T) is absent from gnomAD v4.1 (gnomAD).

CHD7 p.Arg1069Ter

c.3205C>T · rs886040985 · VCV267423

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,784)

Conditions

hypogonadotropic hypogonadism 5 with or without anosmia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 13 of 38
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,784). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD7
Protein: p.Arg1069Ter
Coding: c.3205C>T
MANE Select: NM_017780
dbSNP: rs886040985
Type: single nucleotide variant
Location: chr8:60823843 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1069: the helicase atp-binding domain

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

Disease context

hypogonadotropic hypogonadism 5 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: CHARGE syndrome

Similar variants

CHD7 p.Arg1069Pro Uncertain significance ★ ⚠ same residue
CHD7 p.Arg1069= Likely benign ★ same residue
CHD7 p.Arg1069Gln Likely benign ★ same residue
CHD7 p.Arg1069Gly 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

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-arg1069ter (accessed [today's date]).

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