Is CHD2 p.Gln148Pro (c.443A>C) pathogenic?

CHD2 p.Gln148Pro (c.443A>C) is classified Uncertain significance in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-17). AlphaMissense: likely benign (0.0627); Very rare (popmax 0.00111%, sas).

How common is CHD2 p.Gln148Pro (c.443A>C) in the general population?

CHD2 p.Gln148Pro (c.443A>C) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about CHD2 p.Gln148Pro (c.443A>C)?

AlphaMissense predicts likely benign (score 0.0627) — an in-silico prediction, not a clinical call.

CHD2 p.Gln148Pro

c.443A>C · rs2141755353 · VCV1690493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0627	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.3	GERP 2.9, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 11 kb · p 0.18 · regional, not allelic
Overall
CADD	22.9	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 0.00111% South Asian · 1/89,696 alleles

Overall 0.000138% 2/1,452,078 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	89,696
European (non-Finnish)	8.52e-05%	1,174,198

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.Gln148Pro
Coding: c.443A>C
MANE Select: NM_001271
dbSNP: rs2141755353
Type: single nucleotide variant
Location: chr15:92929091 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 148: a UniProt-annotated variant site (in dee94); the 'disordered' region

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

Similar variants

CHD2 p.Gln148Ter Pathogenic ★ 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
CHD2 c.693-1G>A Likely pathogenic ★★ same type
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ same type
CHD2 p.Arg1072Ter 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-gln148pro (accessed [today's date]).

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