Is CHML p.Arg369Gln (c.1106G>A) pathogenic?

CHML p.Arg369Gln (c.1106G>A) is classified Uncertain significance in CHML (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.1421); Very rare (popmax 0.00534%, afr).

How common is CHML p.Arg369Gln (c.1106G>A) in the general population?

CHML p.Arg369Gln (c.1106G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CHML p.Arg369Gln (c.1106G>A)?

AlphaMissense predicts likely benign (score 0.1421) — an in-silico prediction, not a clinical call.

CHML p.Arg369Gln

c.1106G>A · VCV4002419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1421	likely benign
REVEL	0.699	pathogenic-leaning
SaProt	LLR -11.68	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 1.7	GERP 2, phastCons 0.29
Regional constraint	o/e 1.03	unconstrained · MANE · 1,967 bp · p 0.34 · regional, not allelic
Overall
CADD	24.5	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 0.00534% African / African-American · 4/74,882 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,794 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,720
East Asian	0.00223%	44,892
Admixed American	0.00167%	59,972
European (non-Finnish)	0.00136%	73,744

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: CHML
Protein: p.Arg369Gln
Coding: c.1106G>A
MANE Select: NM_001381853
Type: single nucleotide variant
Location: chr1:241634661 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77

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

Similar variants

OPN3 p.Leu80= Benign ★★ same type
CHML p.Ala105Thr Uncertain significance ★ ⚠ same type
CHML p.Ala105Val Uncertain significance ★ ⚠ same type
CHML p.Ala24Gly Uncertain significance ★ ⚠ same type
CHML p.Ala267Pro Uncertain significance ★ ⚠ same type
CHML p.Ala26Pro Uncertain significance ★ ⚠ same type
CHML p.Ala2Val Uncertain significance ★ ⚠ same type
CHML p.Ala627Thr 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/chml-p-arg369gln (accessed [today's date]).

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