Is CHD7 p.Arg2495Ser (c.7485G>T) pathogenic?

CHD7 p.Arg2495Ser (c.7485G>T) is classified Benign/Likely benign in CHD7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-29). AlphaMissense: likely benign (0.3368); Rare (popmax 0.2%, sas); Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.Arg2495Ser (c.7485G>T)?

CHD7 p.Arg2495Ser (c.7485G>T) is associated with hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome (ClinVar).

How common is CHD7 p.Arg2495Ser (c.7485G>T) in the general population?

CHD7 p.Arg2495Ser (c.7485G>T) is rare (popmax 0.2%, sas) (gnomAD).

What do computational predictors say about CHD7 p.Arg2495Ser (c.7485G>T)?

AlphaMissense predicts likely benign (score 0.3368) — an in-silico prediction, not a clinical call.

CHD7 p.Arg2495Ser

c.7485G>T · rs547209998 · VCV1234328

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.3368 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.2%, sas)

Conditions

hypogonadotropic hypogonadism 5 with or without anosmia

Computational evidence

Protein change
AlphaMissense	0.3368	likely benign
REVEL	0.399	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.89, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 17 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.2% South Asian · 182/91,074 alleles

Filtering AF 0.176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.0123% 199/1,613,980 alleles · rare exomes 186/1,461,682 · genomes 13/152,298 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.2%	500
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00266%	37,524
European (non-Finnish)	0.00017%	589,939

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.Arg2495Ser
Coding: c.7485G>T
MANE Select: NM_017780
dbSNP: rs547209998
Type: single nucleotide variant
Location: chr8:60856765 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2495: a UniProt-annotated variant site (in charges; uncertain significance)

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.Arg2495Gly 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
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-arg2495ser (accessed [today's date]).

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