Is ACACB p.Ser677Asn (c.2030G>A) pathogenic?

ACACB p.Ser677Asn (c.2030G>A) is classified Likely benign in ACACB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). AlphaMissense: likely benign (0.1155); Ultra-rare (popmax 0.01%, nfe).

How common is ACACB p.Ser677Asn (c.2030G>A) in the general population?

ACACB p.Ser677Asn (c.2030G>A) is ultra-rare (popmax 0.01%, nfe) (gnomAD).

What do computational predictors say about ACACB p.Ser677Asn (c.2030G>A)?

AlphaMissense predicts likely benign (score 0.1155) — an in-silico prediction, not a clinical call.

ACACB p.Ser677Asn

c.2030G>A · rs373217436 · VCV2219339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1155 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1155	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -4.17	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 -0.72	GERP -3.8
Regional constraint	o/e 0.88	unconstrained · MANE · 111 kb · p 4.8e-09 · regional, not allelic
Overall
CADD	8.938	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 0.01% European (non-Finnish) · 118/1,179,354 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00796%

Overall 0.00775% 125/1,613,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.01%	9,995
Remaining individualsnot grpmax-eligible	0.00801%	12,492
South Asian	0.0022%	45,533

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: ACACB
Protein: p.Ser677Asn
Coding: c.2030G>A
MANE Select: NM_001093
dbSNP: rs373217436
Type: single nucleotide variant
Location: chr12:109188048 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.29 · 11 PDB
Residue 677: the biotin carboxylation domain

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

Similar variants

ACACB p.Val958Met Uncertain significance ★★ ⚠ same type
ACACB c.6942+9C>T Benign ★★ same type
ACACB c.6943-8G>A Benign ★★ same type
ACACB c.7113+7C>T Benign/Likely benign ★★ same type
ACACB p.Ala650= Likely benign ★★ same type
ACACB p.Arg1786Gln Likely benign ★★ ⚠ same type
ACACB p.Asp1481Val Benign/Likely benign ★★ ⚠ same type
ACACB p.Gln1257Glu 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/acacb-p-ser677asn (accessed [today's date]).

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