Is CHM p.Ile614Val (c.1840A>G) pathogenic?

CHM p.Ile614Val (c.1840A>G) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.1169); Very rare (popmax 0.00123%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Ile614Val (c.1840A>G)?

CHM p.Ile614Val (c.1840A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHM p.Ile614Val (c.1840A>G) in the general population?

CHM p.Ile614Val (c.1840A>G) is very rare (popmax 0.00123%, nfe) (gnomAD).

What do computational predictors say about CHM p.Ile614Val (c.1840A>G)?

AlphaMissense predicts likely benign (score 0.1169) — an in-silico prediction, not a clinical call.

CHM p.Ile614Val

c.1840A>G · VCV3833047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1169 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00123%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1169	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.63, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	16.13	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 0.00123% European (non-Finnish) · 11/893,287 alleles

Filtering AF 0.000661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000483%

Overall 0.00116% 14/1,206,815 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00632%	15,828
European (non-Finnish)grpmax	0.00123%	81,208

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CHM
Protein: p.Ile614Val
Coding: c.1840A>G
MANE Select: NM_000390
Type: single nucleotide variant
Location: chrX:85864752 (GRCh38)
Structure: AlphaFold pLDDT 81.05
Residue 614: the 'disordered' region

Full CHM 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

CHM p.Ala123Val Uncertain significance ★★ ⚠ same condition
CHM p.Ala133Thr Uncertain significance ★★ ⚠ same condition
CHM p.Ala166Glu Uncertain significance ★★ ⚠ same condition
CHM p.Arg555Thr Uncertain significance ★★ ⚠ same condition
CHM p.Asn553Asp Uncertain significance ★★ ⚠ same condition
CHM p.Asn610Asp Uncertain significance ★★ ⚠ same condition
CHM p.Asp280His Uncertain significance ★★ ⚠ same condition
CHM p.Gln119Arg 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/chm-p-ile614val (accessed [today's date]).

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