Is CHD3 p.Asn1257Ser (c.3770A>G) pathogenic?

CHD3 p.Asn1257Ser (c.3770A>G) is classified Likely benign in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-25). AlphaMissense: likely benign (0.0574); Ultra-rare (popmax 0.04%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Asn1257Ser (c.3770A>G)?

CHD3 p.Asn1257Ser (c.3770A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHD3 p.Asn1257Ser (c.3770A>G) in the general population?

CHD3 p.Asn1257Ser (c.3770A>G) is ultra-rare (popmax 0.04%, amr) (gnomAD).

What do computational predictors say about CHD3 p.Asn1257Ser (c.3770A>G)?

AlphaMissense predicts likely benign (score 0.0574) — an in-silico prediction, not a clinical call.

CHD3 p.Asn1257Ser

c.3770A>G · VCV3832785

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0574	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 3,550 bp · p 4.9e-38 · regional, not allelic
Overall
CADD	20.6	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 0.04% Admixed American · 24/60,016 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00353% 57/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.04%	2,501
African / African-American	0.00533%	18,752
Remaining individualsnot grpmax-eligible	0.0032%	31,256
East Asian	0.00223%	44,874
European (non-Finnish)	0.0022%	45,385

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: CHD3
Protein: p.Asn1257Ser
Coding: c.3770A>G
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7903867 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1257: a UniProt-annotated variant site (in snibcps)

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD3 p.Asn1257Lys Uncertain significance ★ same residue
CHD3 p.Arg103Ter Pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg966Trp Pathogenic ★★ ⚠ same condition
CHD3 p.Arg985Trp Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Pro1918= Likely pathogenic ★★ same condition
CHD3 p.Arg1266Trp Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg1377Cys Uncertain significance ★★ ⚠ 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/chd3-p-asn1257ser (accessed [today's date]).

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