Is ACER3 p.Pro169Ser (c.505C>T) pathogenic?

ACER3 p.Pro169Ser (c.505C>T) is classified Uncertain significance in ACER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-19). AlphaMissense: likely pathogenic (0.7828); Absent from gnomAD v4.1.

How common is ACER3 p.Pro169Ser (c.505C>T) in the general population?

ACER3 p.Pro169Ser (c.505C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACER3 p.Pro169Ser (c.505C>T)?

AlphaMissense predicts likely pathogenic (score 0.7828) — an in-silico prediction, not a clinical call.

ACER3 p.Pro169Ser

c.505C>T · rs2135323859 · VCV1307145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7828	likely pathogenic
REVEL	0.098	moderately benign-leaning
SaProt	LLR -10.32	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 159 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	24.4	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: ACER3
Protein: p.Pro169Ser
Coding: c.505C>T
MANE Select: NM_018367
dbSNP: rs2135323859
Type: single nucleotide variant
Location: chr11:77015023 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB
Residue 169: an α-helix

Full ACER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACER3 p.Ala2Pro Uncertain significance ★★ ⚠ same type
ACER3 p.Ala4Thr Uncertain significance ★★ ⚠ same type
ACER3 p.Arg62Gln Uncertain significance ★★ ⚠ same type
ACER3 p.Gly12Asp Uncertain significance ★★ ⚠ same type
ACER3 p.Ile97Leu Uncertain significance ★★ ⚠ same type
ACER3 p.Val206Ile Uncertain significance ★★ ⚠ same type
ACER3 c.214+19C>G Benign ★★ same type
ACER3 c.320+14A>C Benign ★★ 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/acer3-p-pro169ser (accessed [today's date]).

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