Is CHM p.Glu113Lys (c.337G>A) pathogenic?

CHM p.Glu113Lys (c.337G>A) is classified Conflicting classifications of pathogenicity in CHM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-26). AlphaMissense: likely benign (0.0901); Ultra-rare (popmax 0.0231%, mid); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Glu113Lys (c.337G>A)?

CHM p.Glu113Lys (c.337G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CHM p.Glu113Lys (c.337G>A) in the general population?

CHM p.Glu113Lys (c.337G>A) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

What do computational predictors say about CHM p.Glu113Lys (c.337G>A)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

CHM p.Glu113Lys

c.337G>A · rs754548037 · VCV2174214

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -7.52	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 2.5	GERP 2.8, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	19.55	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 0.0231% Middle Eastern · 1/4,333 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00249% 30/1,206,543 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,333
South Asian	0.00355%	28,133
African / African-American	0.00352%	28,392
East Asian	0.00297%	33,718
European (non-Finnish)	0.00246%	40,620
Admixed American	0.00221%	45,350
Remaining individualsnot grpmax-eligible	0.0021%	47,509

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.Glu113Lys
Coding: c.337G>A
MANE Select: NM_000390
dbSNP: rs754548037
Type: single nucleotide variant
Location: chrX:85964030 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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.Glu113Gly Likely benign ★★ ⚠ same residue
CHM p.Glu113= Likely benign ★ same residue
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

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-glu113lys (accessed [today's date]).

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