Is ACER1 p.Phe203Ser (c.608T>C) pathogenic?

ACER1 p.Phe203Ser (c.608T>C) is classified Likely benign in ACER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0836); Absent from gnomAD v4.1.

How common is ACER1 p.Phe203Ser (c.608T>C) in the general population?

ACER1 p.Phe203Ser (c.608T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACER1 p.Phe203Ser (c.608T>C)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

ACER1 p.Phe203Ser

c.608T>C · VCV3998158

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.51	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 -0.28	GERP -4.8, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 27 kb · p 0.89 · regional, not allelic
Overall
CADD	5.778	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: ACER1
Protein: p.Phe203Ser
Coding: c.608T>C
MANE Select: NM_133492
Type: single nucleotide variant
Location: chr19:6307171 (GRCh38)
Gene constraint: LOEUF 1.411 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.54

Full ACER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACER1 p.Met221Ile Likely benign ★★ same type
ACER1 p.Ala143Thr Uncertain significance ★ ⚠ same type
ACER1 p.Ala145Gly Uncertain significance ★ ⚠ same type
ACER1 p.Ala181Pro Uncertain significance ★ ⚠ same type
ACER1 p.Ala225Thr Uncertain significance ★ ⚠ same type
ACER1 p.Arg106Cys Uncertain significance ★ ⚠ same type
ACER1 p.Arg117Ser Uncertain significance ★ ⚠ same type
ACER1 p.Arg122His 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/acer1-p-phe203ser (accessed [today's date]).

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