Is CHD7 p.Ile43Val (c.127A>G) pathogenic?

CHD7 p.Ile43Val (c.127A>G) is classified Conflicting classifications of pathogenicity in CHD7 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-06-12). AlphaMissense: likely benign (0.0604); Ultra-rare (popmax 0.0851%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Ile43Val (c.127A>G)?

CHD7 p.Ile43Val (c.127A>G) is associated with Inborn genetic diseases, CHARGE syndrome, hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

How common is CHD7 p.Ile43Val (c.127A>G) in the general population?

CHD7 p.Ile43Val (c.127A>G) is ultra-rare (popmax 0.0851%, amr) (gnomAD).

What do computational predictors say about CHD7 p.Ile43Val (c.127A>G)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

CHD7 p.Ile43Val

c.127A>G · rs201542180 · VCV588812

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0851%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -2.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.84 · regional, not allelic
Overall
CADD	18.31	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 0.0851% Admixed American · 51/59,962 alleles

Filtering AF 0.0664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0598%

Overall 0.0178% 287/1,613,536 alleles · ultra-rare exomes 275/1,461,306 · genomes 12/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0851%	1,176
South Asian	0.066%	1,516
Middle Eastern	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0224%	4,461
European (non-Finnish)	0.013%	7,711
Finnishnot grpmax-eligible	0.00469%	21,336
African / African-American	0.004%	24,980
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588

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.Ile43Val
Coding: c.127A>G
MANE Select: NM_017780
dbSNP: rs201542180
Type: single nucleotide variant
Location: chr8:60741559 (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

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 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
CHD7 c.3202-3T>G 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-ile43val (accessed [today's date]).

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