Is CHD2 p.Gln1702Pro (c.5105A>C) pathogenic?

CHD2 p.Gln1702Pro (c.5105A>C) is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely benign (0.0597); Very rare (popmax 8.47e-05%, nfe).

How common is CHD2 p.Gln1702Pro (c.5105A>C) in the general population?

CHD2 p.Gln1702Pro (c.5105A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHD2 p.Gln1702Pro (c.5105A>C)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

CHD2 p.Gln1702Pro

c.5105A>C · rs1064796157 · VCV1695502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.282	benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,988 bp · p 0.77 · regional, not allelic
Overall
CADD	18.86	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,004 alleles

Overall 6.84e-05% 1/1,461,888 alleles · very rare

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: CHD2
Protein: p.Gln1702Pro
Coding: c.5105A>C
MANE Select: NM_001271
dbSNP: rs1064796157
Type: single nucleotide variant
Location: chr15:93020210 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1702: the 'disordered' region; a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)

Full CHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD2 p.Gln1702Arg Uncertain significance ★★ ⚠ same residue
CHD2 p.Gln1702= Benign/Likely benign ★★ same residue
CHD2 p.Gln1702Glu Benign ★ same residue
CHD2 p.Gln1702fs Uncertain significance ★ same residue
CHD2 c.1153+1G>C Pathogenic ★★ same type
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD2 c.294+1G>T Likely pathogenic ★★ same type
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ 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/chd2-p-gln1702pro (accessed [today's date]).

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