Is CHD7 p.Ala173Val (c.518C>T) pathogenic?

CHD7 p.Ala173Val (c.518C>T) is classified Conflicting classifications of pathogenicity in CHD7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-20). AlphaMissense: likely benign (0.081); Very rare (popmax 0.00167%, amr); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ala173Val (c.518C>T)?

CHD7 p.Ala173Val (c.518C>T) is associated with CHARGE syndrome, hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

How common is CHD7 p.Ala173Val (c.518C>T) in the general population?

CHD7 p.Ala173Val (c.518C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHD7 p.Ala173Val (c.518C>T)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

CHD7 p.Ala173Val

c.518C>T · rs759229667 · VCV2962477

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.051	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 4.1	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.84 · regional, not allelic
Overall
CADD	21.2	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 0.00167% Admixed American · 1/59,968 alleles

Overall 0.000124% 2/1,613,638 alleles · very rare exomes 2/1,461,354 · genomes 0/152,284 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,968
European (non-Finnish)	8.48e-05%	1,179,764

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.Ala173Val
Coding: c.518C>T
MANE Select: NM_017780
dbSNP: rs759229667
Type: single nucleotide variant
Location: chr8:60741950 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 173: the 'disordered' region

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

Disease context

CHARGE syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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-ala173val (accessed [today's date]).

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