Is FARSA p.Ala7Val (c.20C>T) pathogenic?

FARSA p.Ala7Val (c.20C>T) is classified Uncertain significance in FARSA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1556); Ultra-rare (popmax 0.0449%, mid).

How common is FARSA p.Ala7Val (c.20C>T) in the general population?

FARSA p.Ala7Val (c.20C>T) is ultra-rare (popmax 0.0449%, mid) (gnomAD).

What do computational predictors say about FARSA p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.1556) — an in-silico prediction, not a clinical call.

FARSA p.Ala7Val

c.20C>T · VCV3513087

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1556 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0449%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1556	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -8.68	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 4.4	GERP 1.6, phastCons 0.87
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.0029 · regional, not allelic
Overall
CADD	12.48	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0449% Middle Eastern · 2/4,452 alleles

Filtering AF 0.00796% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00324%

Overall 0.00312% 49/1,570,204 alleles · ultra-rare exomes 42/1,418,012 · genomes 7/152,192 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0449%	2,226
Ashkenazi Jewishnot grpmax-eligible	0.0139%	7,217
European (non-Finnish)	0.00336%	29,800
Remaining individualsnot grpmax-eligible	0.00329%	30,381
African / African-American	0.0027%	36,972

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_004461
Type: single nucleotide variant
Location: chr19:12933677 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 3 PDB
Residue 7: an α-helix

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

Similar variants

FARSA p.Ala7Ser Uncertain significance ★ ⚠ 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
FARSA p.Ala148Thr 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/farsa-p-ala7val (accessed [today's date]).

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