Is CHP2 p.Ser5Thr (c.14G>C) pathogenic?

CHP2 p.Ser5Thr (c.14G>C) is classified Uncertain significance in CHP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely benign (0.0883); Absent from gnomAD v4.1.

How common is CHP2 p.Ser5Thr (c.14G>C) in the general population?

CHP2 p.Ser5Thr (c.14G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHP2 p.Ser5Thr (c.14G>C)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

CHP2 p.Ser5Thr

c.14G>C · rs939973798 · VCV3144495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -7.68	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 8.2	GERP -0.93, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 2,530 bp · p 0.00038 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHP2
Protein: p.Ser5Thr
Coding: c.14G>C
MANE Select: NM_022097
dbSNP: rs939973798
Type: single nucleotide variant
Location: chr16:23755063 (GRCh38)
Gene constraint: LOEUF 1.653 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.86 · 1 PDB

Full CHP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHP2 p.Ala37Thr Uncertain significance ★ ⚠ same type
CHP2 p.Arg127His Uncertain significance ★ ⚠ same type
CHP2 p.Arg159Cys Uncertain significance ★ ⚠ same type
CHP2 p.Arg159His Uncertain significance ★ ⚠ same type
CHP2 p.Arg193Gly Uncertain significance ★ ⚠ same type
CHP2 p.Arg30Cys Uncertain significance ★ ⚠ same type
CHP2 p.Arg30His Uncertain significance ★ ⚠ same type
CHP2 p.Arg36Trp 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/chp2-p-ser5thr (accessed [today's date]).

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