Is FARSB p.Ala93Pro (c.277G>C) pathogenic?

FARSB p.Ala93Pro (c.277G>C) is classified Benign in FARSB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-29). AlphaMissense: likely benign (0.0897); Rare (popmax 0.626%, afr).

How common is FARSB p.Ala93Pro (c.277G>C) in the general population?

FARSB p.Ala93Pro (c.277G>C) is rare (popmax 0.626%, afr) (gnomAD).

What do computational predictors say about FARSB p.Ala93Pro (c.277G>C)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

FARSB p.Ala93Pro

c.277G>C · rs147487059 · VCV1166427

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.626%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR 1.00	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 -0.069	phastCons 0.17
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	12.19	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 0.626% African / African-American · 444/70,978 alleles

Filtering AF 0.577% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.558%

Overall 0.0358% 531/1,484,046 alleles · rare exomes 238/1,332,014 · genomes 293/152,032 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.626%	160
Admixed American	0.0594%	1,684
Remaining individualsnot grpmax-eligible	0.0433%	2,308
European (non-Finnish)	0.00287%	34,842

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: FARSB
Protein: p.Ala93Pro
Coding: c.277G>C
MANE Select: NM_005687
dbSNP: rs147487059
Type: single nucleotide variant
Location: chr2:222640924 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 93: an α-helix

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

Similar variants

FARSB p.Ala93Ser Uncertain significance ★ ⚠ same residue
FARSB c.848+1G>A Pathogenic/Likely pathogenic ★★ same type
FARSB p.Glu285Lys Pathogenic/Likely pathogenic ★★ same type
FARSB c.716-3C>T Uncertain significance ★★ same type
FARSB p.Ala287Gly Uncertain significance ★★ ⚠ same type
FARSB p.Arg127Cys Uncertain significance ★★ ⚠ same type
FARSB p.Arg127His Uncertain significance ★★ ⚠ same type
FARSB p.Arg135Leu 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/farsb-p-ala93pro (accessed [today's date]).

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