Is CNST p.Ser172Pro (c.514T>C) pathogenic?

CNST p.Ser172Pro (c.514T>C) is classified Uncertain significance in CNST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-10). AlphaMissense: likely benign (0.1065); Absent from gnomAD v4.1.

How common is CNST p.Ser172Pro (c.514T>C) in the general population?

CNST p.Ser172Pro (c.514T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNST p.Ser172Pro (c.514T>C)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

CNST p.Ser172Pro

c.514T>C · VCV3494571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.5, phastCons 0.062
Regional constraint	o/e 1.00	unconstrained · MANE · 74 kb · p 0.93 · regional, not allelic
Overall
CADD	14.45	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

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: CNST
Protein: p.Ser172Pro
Coding: c.514T>C
MANE Select: NM_152609
Type: single nucleotide variant
Location: chr1:246621563 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.99

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

Similar variants

CNST p.Ala134Pro Uncertain significance ★ ⚠ same type
CNST p.Ala144Thr Uncertain significance ★ ⚠ same type
CNST p.Ala403Ser Uncertain significance ★ ⚠ same type
CNST p.Ala407Ser Uncertain significance ★ ⚠ same type
CNST p.Ala499Val Uncertain significance ★ ⚠ same type
CNST p.Ala635Val Uncertain significance ★ ⚠ same type
CNST p.Arg115Ile Uncertain significance ★ ⚠ same type
CNST p.Arg115Ser 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/cnst-p-ser172pro (accessed [today's date]).

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