Is IQCE p.Val575= (c.1725G>T) pathogenic?

IQCE p.Val575= (c.1725G>T) is classified Benign in IQCE (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-19). Common (popmax 16.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with polydactyly, postaxial, type a7.

What condition is associated with IQCE p.Val575= (c.1725G>T)?

IQCE p.Val575= (c.1725G>T) is associated with polydactyly, postaxial, type a7 (ClinVar).

IQCE p.Val575=

Q: How common is IQCE p.Val575= (c.1725G>T) in the general population?

IQCE p.Val575= (c.1725G>T) is common (popmax 16.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1725G>T · rs2293405 · VCV1300123

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 16.7%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

polydactyly, postaxial, type a7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP 0.98
Overall
CADD	0.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.7% Middle Eastern · 1,009/6,052 alleles

Filtering AF 15.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.5%

Overall 14% 225,807/1,610,640 alleles · common exomes 206,171/1,458,378 · genomes 19,636/152,262 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	16.7%	6
Ashkenazi Jewishnot grpmax-eligible	15.7%	6
Admixed American	15.6%	6
Amishnot grpmax-eligible	15.2%	7
European (non-Finnish)	14.8%	7
Finnishnot grpmax-eligible	13.8%	7
Remaining individualsnot grpmax-eligible	13.4%	7
African / African-American	10.2%	10
South Asian	9.18%	11
East Asian	7.09%	14

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: IQCE
Protein: p.Val575=
Coding: c.1725G>T
MANE Select: NM_152558
dbSNP: rs2293405
Type: single nucleotide variant
Location: chr7:2604973 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.36
Residue 575: the 'disordered' region

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

Disease context

polydactyly, postaxial, type a7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IQCE p.Val575Met Likely benign ★ same residue
IQCE p.Met1Ile Likely pathogenic ★ same condition
IQCE p.Trp498Ter Pathogenic ★ same condition
IQCE p.Tyr255Ter Pathogenic ★ same condition
IQCE c.825-2A>G Uncertain significance ★ same condition
IQCE p.His615Tyr Uncertain significance ★ ⚠ same condition
IQCE c.1970-5T>C Benign ★ same condition
IQCE c.395-10G>C Benign ★ 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/iqce-p-val575 (accessed [today's date]).

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