Is CHM p.Ser7Leu (c.20C>T) pathogenic?

CHM p.Ser7Leu (c.20C>T) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.1615); Ultra-rare (popmax 0.0229%, mid).

How common is CHM p.Ser7Leu (c.20C>T) in the general population?

CHM p.Ser7Leu (c.20C>T) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

What do computational predictors say about CHM p.Ser7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

CHM p.Ser7Leu

c.20C>T · rs1357495676 · VCV1448456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.464	indeterminate
SaProt	LLR -8.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	23.8	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 0.0229% Middle Eastern · 1/4,368 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000687%

Overall 0.00124% 15/1,206,293 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,368
African / African-American	0.00526%	19,023
European (non-Finnish)	0.00123%	81,174

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.Ser7Leu
Coding: c.20C>T
MANE Select: NM_000390
dbSNP: rs1357495676
Type: single nucleotide variant
Location: chrX:86047513 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

CHM p.Ser7Ter Pathogenic ★ same residue
CHM p.Ser7fs Pathogenic ★ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same type
CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same type
CHM c.1166+1G>A Pathogenic ★★ same type
CHM c.1166+1G>C Pathogenic ★★ same type
CHM c.1167-2A>G Pathogenic ★★ same type
CHM c.1244+1G>A 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/chm-p-ser7leu (accessed [today's date]).

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