Is CHD6 p.Ser999= (c.2997C>T) pathogenic?

CHD6 p.Ser999= (c.2997C>T) is classified Likely benign in CHD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Rare (popmax 0.447%, mid).

How common is CHD6 p.Ser999= (c.2997C>T) in the general population?

CHD6 p.Ser999= (c.2997C>T) is rare (popmax 0.447%, mid) (gnomAD).

CHD6 p.Ser999=

c.2997C>T · rs150157135 · VCV2652335

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.447%, mid)

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 0.21	GERP -1.5, phastCons 0.83
Overall
CADD	5.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.447% Middle Eastern · 23/5,146 alleles

Filtering AF 0.313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.3%

Overall 0.0748% 1,187/1,587,410 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.06%	95
Middle Easterngrpmax	0.447%	224
South Asian	0.345%	290
Remaining individualsnot grpmax-eligible	0.155%	644
Admixed American	0.135%	742
European (non-Finnish)	0.0335%	2,981
African / African-American	0.00677%	14,769
East Asian	0.00227%	44,064

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CHD6
Protein: p.Ser999=
Coding: c.2997C>T
MANE Select: NM_032221
dbSNP: rs150157135
Type: single nucleotide variant
Location: chr20:41455812 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)

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-ser999 (accessed [today's date]).

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