Is PHIP p.Ala126Ser (c.375_376delinsTT) pathogenic?

PHIP p.Ala126Ser (c.375376delinsTT) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-26). No gnomAD frequency available for this variant.

How common is PHIP p.Ala126Ser (c.375_376delinsTT) in the general population?

PHIP p.Ala126Ser (c.375_376delinsTT) is no gnomAD frequency available for this variant (gnomAD).

PHIP p.Ala126Ser

c.375_376delinsTT · rs1554212697 · VCV546473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 51 kb · p 1.8e-17 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHIP
Protein: p.Ala126Ser
Coding: c.375_376delinsTT
MANE Select: NM_017934
dbSNP: rs1554212697
Type: Indel
Location: chr6:79060541 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB

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

Similar variants

PHIP p.Ala126Gly Uncertain significance ★ ⚠ same residue
PHIP p.Thr200fs Pathogenic/Likely pathogenic ★★ same type
PHIP c.122_129+39delinsCGAGGCGGCCCGGGGCGCGGGGCTCAGCTCTCCCCGCTTTGTTGTTGCAGGTGCTGATCCGCGAGAA Likely pathogenic ★ same type
PHIP p.Leu650fs Pathogenic ★ same type
PHIP c.2202-10_2202-8delinsGG Uncertain significance ★ same type
PHIP p.Cys188Arg Uncertain significance ★ same type
PHIP p.Val439Leu 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/phip-p-ala126ser (accessed [today's date]).

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