Is ABCF1 p.Pro677Leu (c.2030C>T) pathogenic?

ABCF1 p.Pro677Leu (c.2030C>T) is classified Uncertain significance in ABCF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-23). AlphaMissense: likely pathogenic (0.6658); Very rare (popmax 0.00534%, nfe).

How common is ABCF1 p.Pro677Leu (c.2030C>T) in the general population?

ABCF1 p.Pro677Leu (c.2030C>T) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about ABCF1 p.Pro677Leu (c.2030C>T)?

AlphaMissense predicts likely pathogenic (score 0.6658) — an in-silico prediction, not a clinical call.

ABCF1 p.Pro677Leu

c.2030C>T · rs762848174 · VCV2369693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6658	likely pathogenic
REVEL	0.896	moderately pathogenic-leaning
SaProt	LLR -14.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 5,079 bp · p 4.6e-11 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00534% European (non-Finnish) · 63/1,180,002 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00434% 70/1,613,638 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0048%	20,827
South Asian	0.00329%	30,360
East Asian	0.00223%	44,892

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: ABCF1
Protein: p.Pro677Leu
Coding: c.2030C>T
MANE Select: NM_001025091
dbSNP: rs762848174
Type: single nucleotide variant
Location: chr6:30586710 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 677: the abc transporter 2 domain

Full ABCF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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ABCF1 p.Ala251Thr Uncertain significance ★ ⚠ same type
ABCF1 p.Ala276Val Uncertain significance ★ ⚠ same type
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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/abcf1-p-pro677leu (accessed [today's date]).

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