Is FAR1 p.Pro169Ser (c.505C>T) pathogenic?

FAR1 p.Pro169Ser (c.505C>T) is classified Uncertain significance in FAR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.138); Very rare (popmax 0.00679%, amr); Associated with Inborn genetic diseases.

What condition is associated with FAR1 p.Pro169Ser (c.505C>T)?

FAR1 p.Pro169Ser (c.505C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FAR1 p.Pro169Ser (c.505C>T) in the general population?

FAR1 p.Pro169Ser (c.505C>T) is very rare (popmax 0.00679%, amr) (gnomAD).

What do computational predictors say about FAR1 p.Pro169Ser (c.505C>T)?

AlphaMissense predicts likely benign (score 0.138) — an in-silico prediction, not a clinical call.

FAR1 p.Pro169Ser

c.505C>T · rs761885527 · VCV1923217

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.138 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00679%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.138	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -7.82	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 6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 34 kb · p 2.6e-21 · regional, not allelic
Overall
CADD	23.9	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 0.00679% Admixed American · 4/58,914 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000249% 4/1,606,626 alleles · very rare exomes 4/1,454,376 · genomes 0/152,250 · joint denominator

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: FAR1
Protein: p.Pro169Ser
Coding: c.505C>T
MANE Select: NM_032228
dbSNP: rs761885527
Type: single nucleotide variant
Location: chr11:13708039 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 169: a UniProt-annotated variant site (in pfcrd; results in a complete loss of enzyme activity)

Full FAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FAR1 p.Pro169Leu Uncertain significance ★★ ⚠ same residue
FAR1 p.Pro169Thr Uncertain significance ★ ⚠ same residue
FAR1 p.Arg160Cys Uncertain significance ★★ ⚠ same condition
FAR1 p.Arg160His Uncertain significance ★★ ⚠ same condition
FAR1 p.Arg336Lys Uncertain significance ★★ ⚠ same condition
FAR1 p.Arg337Gln Uncertain significance ★★ same condition
FAR1 p.Arg467His Uncertain significance ★★ ⚠ same condition
FAR1 p.Arg508Gln Uncertain significance ★★ same condition

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/far1-p-pro169ser (accessed [today's date]).

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