Is CHD5 p.Pro702Leu (c.2105C>T) pathogenic?

CHD5 p.Pro702Leu (c.2105C>T) is classified Uncertain significance in CHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.2515); Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD5 p.Pro702Leu (c.2105C>T)?

CHD5 p.Pro702Leu (c.2105C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHD5 p.Pro702Leu (c.2105C>T) in the general population?

CHD5 p.Pro702Leu (c.2105C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about CHD5 p.Pro702Leu (c.2105C>T)?

AlphaMissense predicts likely benign (score 0.2515) — an in-silico prediction, not a clinical call.

CHD5 p.Pro702Leu

c.2105C>T · rs146566155 · VCV2401258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2515	likely benign
REVEL	0.762	pathogenic-leaning
SaProt	LLR -10.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.72	GERP -0.24, phastCons 0.011
Overall
CADD	29.1	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 0.0217% Admixed American · 13/60,012 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00242% 39/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
South Asian	0.00549%	18,218
East Asian	0.00445%	22,447
African / African-American	0.004%	24,983
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00119%	84,289

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.Pro702Leu
Coding: c.2105C>T
MANE Select: NM_004627 · reported on NM_015557
dbSNP: rs146566155
Type: single nucleotide variant
Location: chr1:6142544 (GRCh38)
Structure: AlphaFold pLDDT 78.15 · 4 PDB

Full CHD5 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

CHD5 p.Ala1435Thr Uncertain significance ★★ ⚠ same condition
CHD5 p.Ala1446Ser Uncertain significance ★★ ⚠ same condition
CHD5 p.Ala215Val Uncertain significance ★★ same condition
CHD5 p.Arg1337Cys Uncertain significance ★★ same condition
CHD5 p.Asn21Ser Uncertain significance ★★ ⚠ same condition
CHD5 p.Asp414Asn Uncertain significance ★★ same condition
CHD5 p.Gln979His Uncertain significance ★★ ⚠ same condition
CHD5 p.Glu1302Val 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/chd5-p-pro702leu (accessed [today's date]).

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