Is PEAK1 p.Ser1036Phe (c.3107C>T) pathogenic?

PEAK1 p.Ser1036Phe (c.3107C>T) is classified Uncertain significance in PEAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.0931); Very rare (popmax 0.000254%, nfe).

How common is PEAK1 p.Ser1036Phe (c.3107C>T) in the general population?

PEAK1 p.Ser1036Phe (c.3107C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about PEAK1 p.Ser1036Phe (c.3107C>T)?

AlphaMissense predicts likely benign (score 0.0931) — an in-silico prediction, not a clinical call.

PEAK1 p.Ser1036Phe

c.3107C>T · rs201856196 · VCV2236186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0931	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -7.56	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 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 68 kb · p 0.055 · regional, not allelic
Overall
CADD	23.5	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 0.000254% European (non-Finnish) · 3/1,179,876 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,654 alleles · very rare exomes 2/1,461,444 · genomes 1/152,210 · 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: PEAK1
Protein: p.Ser1036Phe
Coding: c.3107C>T
MANE Select: NM_001385026
dbSNP: rs201856196
Type: single nucleotide variant
Location: chr15:77178820 (GRCh38)
Gene constraint: LOEUF 0.522 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 48.60 · 2 PDB

Full PEAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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PEAK1 p.Ala109Gly Uncertain significance ★ ⚠ same type
PEAK1 p.Ala1135Thr Uncertain significance ★ ⚠ same type
PEAK1 p.Ala1231Thr Uncertain significance ★ ⚠ same type
PEAK1 p.Ala1376Thr Uncertain significance ★ ⚠ same type
PEAK1 p.Ala157Gly Uncertain significance ★ ⚠ same type
PEAK1 p.Ala1659Thr Uncertain significance ★ ⚠ same type
PEAK1 p.Ala402Thr 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/peak1-p-ser1036phe (accessed [today's date]).

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