Is PTPRF p.Ala356Ser (c.1066G>T) pathogenic?

PTPRF p.Ala356Ser (c.1066G>T) is classified Likely benign in PTPRF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0955); Rare (popmax 0.538%, afr).

How common is PTPRF p.Ala356Ser (c.1066G>T) in the general population?

PTPRF p.Ala356Ser (c.1066G>T) is rare (popmax 0.538%, afr) (gnomAD).

What do computational predictors say about PTPRF p.Ala356Ser (c.1066G>T)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

PTPRF p.Ala356Ser

c.1066G>T · rs79621077 · VCV734792

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.538%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -7.10	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 6.8	GERP -0.12, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,728 bp · p 0.011 · regional, not allelic
Overall
CADD	19.46	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 0.538% African / African-American · 404/75,080 alleles

Filtering AF 0.495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.478%

Overall 0.0284% 459/1,613,918 alleles · rare exomes 198/1,461,536 · genomes 261/152,382 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.538%	186
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Admixed American	0.0333%	3,002
South Asian	0.00439%	22,772
European (non-Finnish)	0.000424%	236,008

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: PTPRF
Protein: p.Ala356Ser
Coding: c.1066G>T
MANE Select: NM_002840
dbSNP: rs79621077
Type: single nucleotide variant
Location: chr1:43591088 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 356: a β-strand; the fibronectin type-iii 1 domain

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

Similar variants

PTPRF p.Gly1143Ser Uncertain significance ★★ ⚠ same type
PTPRF p.His1730Gln Uncertain significance ★★ ⚠ same type
PTPRF c.1531+9G>A Benign/Likely benign ★★ same type
PTPRF c.1668+10G>C Benign/Likely benign ★★ same type
PTPRF c.237+5G>A Benign ★★ same type
PTPRF c.3974-9C>T Benign ★★ same type
PTPRF p.Ala1659= Benign ★★ same type
PTPRF p.Ala602= Benign ★★ 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/ptprf-p-ala356ser (accessed [today's date]).

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