Is CHD7 p.Arg1677= (c.5029C>A) pathogenic?

CHD7 p.Arg1677= (c.5029C>A) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-02). Ultra-rare (popmax 0.0267%, amr); Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.Arg1677= (c.5029C>A)?

CHD7 p.Arg1677= (c.5029C>A) is associated with hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome (ClinVar).

How common is CHD7 p.Arg1677= (c.5029C>A) in the general population?

CHD7 p.Arg1677= (c.5029C>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

CHD7 p.Arg1677=

c.5029C>A · rs777652245 · VCV1201277

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, phastCons 0.98
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,012 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000991% 16/1,613,946 alleles · ultra-rare exomes 16/1,461,650 · genomes 0/152,296 · joint denominator

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.Arg1677=
Coding: c.5029C>A
MANE Select: NM_017780
dbSNP: rs777652245
Type: single nucleotide variant
Location: chr8:60845042 (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

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.Arg1677Ter Pathogenic ★★ same residue
CHD7 p.Arg1677Gln Likely benign ★ same residue
CHD7 p.Arg1677Gly 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-arg1677 (accessed [today's date]).

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