Is ACSM2B p.Phe83Ile (c.247T>A) pathogenic?

ACSM2B p.Phe83Ile (c.247T>A) is classified Uncertain significance in ACSM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.6585); Very rare (popmax 0.00167%, amr).

How common is ACSM2B p.Phe83Ile (c.247T>A) in the general population?

ACSM2B p.Phe83Ile (c.247T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ACSM2B p.Phe83Ile (c.247T>A)?

AlphaMissense predicts likely pathogenic (score 0.6585) — an in-silico prediction, not a clinical call.

ACSM2B p.Phe83Ile

c.247T>A · VCV4000980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6585 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6585	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -14.96	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 5	GERP 1.8, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.38 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.00167% Admixed American · 1/59,912 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,460,518 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,912
European (non-Finnish)	0.00017%	589,616

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACSM2B
Protein: p.Phe83Ile
Coding: c.247T>A
MANE Select: NM_001105069
Type: single nucleotide variant
Location: chr16:20559378 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.41

Full ACSM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM2B p.Ile305Val Benign ★★ same type
ACSM2B p.Pro312= Benign ★★ same type
ACSM2B p.Ser272= Benign ★★ same type
ACSM2B p.Ala231Ser Uncertain significance ★ ⚠ same type
ACSM2B p.Ala387Val Uncertain significance ★ ⚠ same type
ACSM2B p.Ala487Asp Uncertain significance ★ ⚠ same type
ACSM2B p.Arg148Lys Uncertain significance ★ ⚠ same type
ACSM2B p.Arg447Gln 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/acsm2b-p-phe83ile (accessed [today's date]).

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