Is CHD9 p.Phe1808Ser (c.5423T>C) pathogenic?

CHD9 p.Phe1808Ser (c.5423T>C) is classified Uncertain significance in CHD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1192); Very rare (popmax 0.00136%, nfe).

How common is CHD9 p.Phe1808Ser (c.5423T>C) in the general population?

CHD9 p.Phe1808Ser (c.5423T>C) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about CHD9 p.Phe1808Ser (c.5423T>C)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

CHD9 p.Phe1808Ser

c.5423T>C · VCV4227955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.559	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.1	GERP -0.24, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	21.1	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 0.00136% European (non-Finnish) · 16/1,179,830 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,613,878 alleles · very rare exomes 16/1,461,622 · genomes 0/152,256 · joint denominator

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: CHD9
Protein: p.Phe1808Ser
Coding: c.5423T>C
MANE Select: NM_001308319
Type: single nucleotide variant
Location: chr16:53292965 (GRCh38)
Gene constraint: LOEUF 0.309 · pLI 1.00 (gnomAD)

Full CHD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD9 c.6620-2A>C Uncertain significance ★ same type
CHD9 p.Ala1363Thr Uncertain significance ★ ⚠ same type
CHD9 p.Ala1408Val Uncertain significance ★ ⚠ same type
CHD9 p.Ala1537Thr Uncertain significance ★ same type
CHD9 p.Ala167Val Uncertain significance ★ same type
CHD9 p.Ala1724Gly Uncertain significance ★ same type
CHD9 p.Ala1742Val Uncertain significance ★ same type
CHD9 p.Ala1938Thr Uncertain significance ★ ⚠ 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/chd9-p-phe1808ser (accessed [today's date]).

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