Is IQGAP1 p.Lys891Gln (c.2671A>C) pathogenic?

IQGAP1 p.Lys891Gln (c.2671A>C) is classified Uncertain significance in IQGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.1122); Ultra-rare (popmax 0.0586%, nfe).

How common is IQGAP1 p.Lys891Gln (c.2671A>C) in the general population?

IQGAP1 p.Lys891Gln (c.2671A>C) is ultra-rare (popmax 0.0586%, nfe) (gnomAD).

What do computational predictors say about IQGAP1 p.Lys891Gln (c.2671A>C)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

IQGAP1 p.Lys891Gln

c.2671A>C · rs142816966 · VCV2363160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0586%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -7.90	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 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 86 kb · p 0.1 · regional, not allelic
Overall
CADD	23.3	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 0.0586% European (non-Finnish) · 691/1,179,908 alleles

Filtering AF 0.0549% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0535%

Overall 0.0469% 757/1,614,060 alleles · ultra-rare exomes 702/1,461,766 · genomes 55/152,294 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.877%	114
European (non-Finnish)grpmax	0.0586%	1,708
Admixed American	0.055%	1,819
Remaining individualsnot grpmax-eligible	0.0304%	3,290
African / African-American	0.00533%	18,760
East Asian	0.00223%	44,896
Finnishnot grpmax-eligible	0.00156%	64,038

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: IQGAP1
Protein: p.Lys891Gln
Coding: c.2671A>C
MANE Select: NM_003870
dbSNP: rs142816966
Type: single nucleotide variant
Location: chr15:90474580 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.64 · 5 PDB

Full IQGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IQGAP1 c.390+5C>T Benign ★★ same type
IQGAP1 p.Glu1326= Benign ★★ same type
IQGAP1 c.2179-2A>T Uncertain significance ★ same type
IQGAP1 p.Ala13Val Uncertain significance ★ ⚠ same type
IQGAP1 p.Ala1511Thr Uncertain significance ★ ⚠ same type
IQGAP1 p.Ala216Thr Uncertain significance ★ ⚠ same type
IQGAP1 p.Ala239Val Uncertain significance ★ ⚠ same type
IQGAP1 p.Ala308Thr 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/iqgap1-p-lys891gln (accessed [today's date]).

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