Is ACOD1 p.Ser61Arg (c.183T>G) pathogenic?

ACOD1 p.Ser61Arg (c.183T>G) is classified Likely benign in ACOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.2886); Ultra-rare (popmax 0.0735%, eas).

How common is ACOD1 p.Ser61Arg (c.183T>G) in the general population?

ACOD1 p.Ser61Arg (c.183T>G) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about ACOD1 p.Ser61Arg (c.183T>G)?

AlphaMissense predicts likely benign (score 0.2886) — an in-silico prediction, not a clinical call.

ACOD1 p.Ser61Arg

c.183T>G · rs192457026 · VCV2643848

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2886 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2886	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -7.18	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 -0.84	GERP -2
Regional constraint	o/e 0.90	unconstrained · MANE · 9,423 bp · p 0.02 · regional, not allelic
Overall
CADD	15.22	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 0.0735% East Asian · 30/40,836 alleles

Filtering AF 0.0529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0458%

Overall 0.113% 1,753/1,544,678 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.82%	55
Ashkenazi Jewishnot grpmax-eligible	0.675%	148
Remaining individualsnot grpmax-eligible	0.127%	790
East Asiangrpmax	0.0735%	1,361
South Asian	0.0513%	1,949
Middle Eastern	0.0335%	2,987
European (non-Finnish)	0.0293%	3,408
African / African-American	0.00137%	73,070

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACOD1
Protein: p.Ser61Arg
Coding: c.183T>G
MANE Select: NM_001258406
dbSNP: rs192457026
Type: single nucleotide variant
Location: chr13:76953608 (GRCh38)
Gene constraint: LOEUF 1.53 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.45 · 6 PDB

Full ACOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOD1 p.Arg273His Benign ★★ same type
ACOD1 p.Asn152Ser Benign ★★ same type
ACOD1 p.Pro77= Benign ★★ same type
ACOD1 c.265-3C>T 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/acod1-p-ser61arg (accessed [today's date]).

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