Is FARSA p.Arg144Pro (c.431G>C) pathogenic?

FARSA p.Arg144Pro (c.431G>C) is classified Uncertain significance in FARSA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: ambiguous (0.5574); Ultra-rare (popmax 0.0109%, nfe).

How common is FARSA p.Arg144Pro (c.431G>C) in the general population?

FARSA p.Arg144Pro (c.431G>C) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

What do computational predictors say about FARSA p.Arg144Pro (c.431G>C)?

AlphaMissense predicts ambiguous (score 0.5574) — an in-silico prediction, not a clinical call.

FARSA p.Arg144Pro

c.431G>C · VCV4667054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5574	ambiguous
REVEL	0.054	moderately benign-leaning
SaProt	LLR -12.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.3
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.0029 · regional, not allelic
Overall
CADD	10.77	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 0.0109% European (non-Finnish) · 129/1,180,010 alleles

Filtering AF 0.00936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0088%

Overall 0.00843% 136/1,613,974 alleles · ultra-rare exomes 131/1,461,788 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0109%	9,147
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asian	0.0022%	45,547
Admixed American	0.00167%	59,994

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: FARSA
Protein: p.Arg144Pro
Coding: c.431G>C
MANE Select: NM_004461
Type: single nucleotide variant
Location: chr19:12930295 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 3 PDB
Residue 144: an α-helix

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

Similar variants

FARSA p.Arg144Trp Uncertain significance ★ ⚠ same residue
FARSA p.Arg144Gln Likely benign ★ same residue
FARSA p.Pro347Leu Likely pathogenic ★★ same type
FARSA p.Arg338Cys Uncertain significance ★★ ⚠ same type
FARSA p.Gly306Ser Uncertain significance ★★ ⚠ same type
FARSA c.1027-17T>C Benign ★★ same type
FARSA p.Arg271His Pathogenic ★ same type
FARSA p.Phe256Leu Pathogenic ★ 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/farsa-p-arg144pro (accessed [today's date]).

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