Is CHD6 p.Phe72Cys (c.215T>G) pathogenic?

CHD6 p.Phe72Cys (c.215T>G) is classified Uncertain significance in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely benign (0.0959); Absent from gnomAD v4.1.

How common is CHD6 p.Phe72Cys (c.215T>G) in the general population?

CHD6 p.Phe72Cys (c.215T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD6 p.Phe72Cys (c.215T>G)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

CHD6 p.Phe72Cys

c.215T>G · rs766357098 · VCV2613144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.346	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 38 kb · p 0.49 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD6
Protein: p.Phe72Cys
Coding: c.215T>G
MANE Select: NM_032221
dbSNP: rs766357098
Type: single nucleotide variant
Location: chr20:41533389 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Residue 72: the 'required for dna-dependent atpase activity' region; the 'disordered' region

Full CHD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD6 c.1858-19G>A Benign ★★ same type
CHD6 c.554+5G>A Benign/Likely benign ★★ same type
CHD6 c.852+4T>C Benign ★★ same type
CHD6 p.Ala1205Gly Benign ★★ same type
CHD6 p.Arg2389Cys Benign ★★ same type
CHD6 p.Glu1271= Benign ★★ same type
CHD6 p.Glu2404Gln Benign ★★ same type
CHD6 p.Gly1519Asp Benign ★★ same type

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/chd6-p-phe72cys (accessed [today's date]).

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