Is CHD5 p.Ser151Leu (c.452C>T) pathogenic?

CHD5 p.Ser151Leu (c.452C>T) is classified Likely benign in CHD5 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-01). AlphaMissense: likely benign (0.2433); Rare (popmax 0.61%, mid).

How common is CHD5 p.Ser151Leu (c.452C>T) in the general population?

CHD5 p.Ser151Leu (c.452C>T) is rare (popmax 0.61%, mid) (gnomAD).

What do computational predictors say about CHD5 p.Ser151Leu (c.452C>T)?

AlphaMissense predicts likely benign (score 0.2433) — an in-silico prediction, not a clinical call.

CHD5 p.Ser151Leu

c.452C>T · rs150062924 · VCV3025017

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2433 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.61%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2433	likely benign
REVEL	0.517	indeterminate
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.61% Middle Eastern · 37/6,062 alleles

Filtering AF 0.455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.401%

Overall 0.162% 2,621/1,614,088 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.61%	164
European (non-Finnish)	0.191%	524
Remaining individualsnot grpmax-eligible	0.19%	525
Admixed American	0.143%	698
South Asian	0.0922%	1,084
African / African-American	0.052%	1,924
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
Finnishnot grpmax-eligible	0.00469%	21,343
East Asian	0.00223%	44,882

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: CHD5
Protein: p.Ser151Leu
Coding: c.452C>T
MANE Select: NM_004627 · reported on NM_015557
dbSNP: rs150062924
Type: single nucleotide variant
Location: chr1:6155653 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB

Full CHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD5 c.4171+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD5 p.Arg1618Ter Pathogenic/Likely pathogenic ★★ same type
CHD5 p.Arg193Trp Pathogenic/Likely pathogenic ★★ same type
CHD5 p.Pro1124Leu Pathogenic/Likely pathogenic ★★ same type
CHD5 p.Ser912Phe Pathogenic/Likely pathogenic ★★ same type
CHD5 c.2043+4A>T Uncertain significance ★★ same type
CHD5 c.79+5G>A Uncertain significance ★★ same type
CHD5 p.Ala1435Thr 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/chd5-p-ser151leu (accessed [today's date]).

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