Is ACCS p.Arg48His (c.143G>A) pathogenic?

ACCS p.Arg48His (c.143G>A) is classified Uncertain significance in ACCS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0657); Ultra-rare (popmax 0.0535%, eas).

How common is ACCS p.Arg48His (c.143G>A) in the general population?

ACCS p.Arg48His (c.143G>A) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about ACCS p.Arg48His (c.143G>A)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

ACCS p.Arg48His

c.143G>A · rs367984824 · VCV3136093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.90	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 -0.3	GERP -2.7
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.26 · regional, not allelic
Overall
CADD	6.488	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,896 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00229% 37/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,871
Remaining individualsnot grpmax-eligible	0.0112%	8,927
South Asian	0.00329%	30,363
African / African-American	0.00267%	37,461
European (non-Finnish)	8.47e-05%	1,180,040

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: ACCS
Protein: p.Arg48His
Coding: c.143G>A
MANE Select: NM_032592
dbSNP: rs367984824
Type: single nucleotide variant
Location: chr11:44067770 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63

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

Similar variants

ACCS p.Arg48Cys Uncertain significance ★ ⚠ same residue
ACCS p.Arg489Cys Benign ★★ same type
ACCS p.Val202= Benign ★★ same type
ACCS p.Ala11Val Uncertain significance ★ ⚠ same type
ACCS p.Ala237Thr Uncertain significance ★ ⚠ same type
ACCS p.Ala77Ser Uncertain significance ★ ⚠ same type
ACCS p.Arg124Lys Uncertain significance ★ ⚠ same type
ACCS p.Arg142Gln 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/accs-p-arg48his (accessed [today's date]).

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