Is DCHS2 p.Pro1295Ser (c.3883C>T) pathogenic?

DCHS2 p.Pro1295Ser (c.3883C>T) is classified Uncertain significance in DCHS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.207); Absent from gnomAD v4.1.

How common is DCHS2 p.Pro1295Ser (c.3883C>T) in the general population?

DCHS2 p.Pro1295Ser (c.3883C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCHS2 p.Pro1295Ser (c.3883C>T)?

AlphaMissense predicts likely benign (score 0.207) — an in-silico prediction, not a clinical call.

DCHS2 p.Pro1295Ser

c.3883C>T · VCV3500055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.207 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.207	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -9.65	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 257 kb · p 0.063 · regional, not allelic
Overall
CADD	21.4	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: DCHS2
Protein: p.Pro1295Ser
Coding: c.3883C>T
MANE Select: NM_001358235
Type: single nucleotide variant
Location: chr4:154329558 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)

Full DCHS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCHS2 c.2053-13744T>A Uncertain significance ★ same type
DCHS2 c.2053-13798T>C Uncertain significance ★ same type
DCHS2 c.2053-13820G>A Uncertain significance ★ same type
DCHS2 c.2053-13834C>G Uncertain significance ★ same type
DCHS2 c.2244+3317A>T Uncertain significance ★ same type
DCHS2 c.2476+8901A>C Uncertain significance ★ same type
DCHS2 c.2477-1G>T Uncertain significance ★ same type
DCHS2 c.3730+872C>T 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/dchs2-p-pro1295ser (accessed [today's date]).

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