Is CSH1 p.Asp37Glu (c.111C>A) pathogenic?

CSH1 p.Asp37Glu (c.111C>A) is classified Uncertain significance in CSH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.1815); Rare (popmax 0.593%, afr).

How common is CSH1 p.Asp37Glu (c.111C>A) in the general population?

CSH1 p.Asp37Glu (c.111C>A) is rare (popmax 0.593%, afr) (gnomAD).

What do computational predictors say about CSH1 p.Asp37Glu (c.111C>A)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

CSH1 p.Asp37Glu

c.111C>A · rs1282514914 · VCV2344799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.593%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.44	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 0.79	GERP -2.9, phastCons 0.99
Regional constraint	o/e 0.10	constrained · MANE · 117 bp · p 2.1e-08 · regional, not allelic
Overall
CADD	2.103	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 0.593% African / African-American · 97/16,366 alleles

Filtering AF 0.497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.462%

Overall 0.018% 130/720,546 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.593%	169
Middle Eastern	0.0412%	2,428
Admixed American	0.0328%	3,050
Remaining individualsnot grpmax-eligible	0.0303%	3,305
South Asian	0.0056%	17,866
European (non-Finnish)	0.00197%	50,633

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: CSH1
Protein: p.Asp37Glu
Coding: c.111C>A
MANE Select: NM_001317
dbSNP: rs1282514914
Type: single nucleotide variant
Location: chr17:63896135 (GRCh38)
Gene constraint: LOEUF 1.213 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.67 · 1 PDB
Residue 37: an α-helix

Full CSH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSH1 p.Ala14Gly Uncertain significance ★ ⚠ same type
CSH1 p.Ala2Thr Uncertain significance ★ ⚠ same type
CSH1 p.Arg159His Uncertain significance ★ ⚠ same type
CSH1 p.Arg160Trp Uncertain significance ★ ⚠ same type
CSH1 p.Arg204Ser Uncertain significance ★ ⚠ same type
CSH1 p.Arg6Gln Uncertain significance ★ ⚠ same type
CSH1 p.Asp135Asn Uncertain significance ★ ⚠ same type
CSH1 p.Asp180His 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/csh1-p-asp37glu (accessed [today's date]).

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