Is ACER3 p.Phe111Ser (c.332T>C) pathogenic?

ACER3 p.Phe111Ser (c.332T>C) is classified Uncertain significance in ACER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.9075); Absent from gnomAD v4.1.

How common is ACER3 p.Phe111Ser (c.332T>C) in the general population?

ACER3 p.Phe111Ser (c.332T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACER3 p.Phe111Ser (c.332T>C)?

AlphaMissense predicts likely pathogenic (score 0.9075) — an in-silico prediction, not a clinical call.

ACER3 p.Phe111Ser

c.332T>C · VCV3702021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9075 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,567,192)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9075	likely pathogenic
REVEL	0.274	benign-leaning
SaProt	LLR -2.95	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 159 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	24.9	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

No allele count reported in gnomAD v4.1 (AN 1,567,192). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACER3
Protein: p.Phe111Ser
Coding: c.332T>C
MANE Select: NM_018367
Type: single nucleotide variant
Location: chr11:76985654 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB

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-phe111ser (accessed [today's date]).

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