Is KRT16 p.Asp110Val (c.329A>T) pathogenic?

KRT16 p.Asp110Val (c.329A>T) is classified Uncertain significance in KRT16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.594); Very rare (popmax 0.000763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT16 p.Asp110Val (c.329A>T)?

KRT16 p.Asp110Val (c.329A>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT16 p.Asp110Val (c.329A>T) in the general population?

KRT16 p.Asp110Val (c.329A>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about KRT16 p.Asp110Val (c.329A>T)?

AlphaMissense predicts likely pathogenic (score 0.594) — an in-silico prediction, not a clinical call.

KRT16 p.Asp110Val

c.329A>T · VCV4094720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.594 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.594	likely pathogenic
REVEL	0.208	benign-leaning
SaProt	LLR -11.65	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.16	GERP -3.7, phastCons 0.003
Regional constraint	o/e 0.89	unconstrained · MANE · 2,750 bp · p 0.0085 · regional, not allelic
Overall
CADD	17.5	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 0.000763% European (non-Finnish) · 9/1,180,014 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,906 alleles · very rare exomes 10/1,461,878 · genomes 1/152,028 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)grpmax	0.000763%	131,113

Remaining individuals 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: KRT16
Protein: p.Asp110Val
Coding: c.329A>T
MANE Select: NM_005557
Type: single nucleotide variant
Location: chr17:41612360 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.26
Residue 110: the 'head' region

Full KRT16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT16 p.Arg290His Uncertain significance ★★ ⚠ same condition
KRT16 p.Glu442Lys Uncertain significance ★★ ⚠ same condition
KRT16 p.Trp152Ser Uncertain significance ★★ ⚠ same condition
KRT16 p.Ala355Ser Uncertain significance ★ ⚠ same condition
KRT16 p.Ala415Val Uncertain significance ★ ⚠ same condition
KRT16 p.Ala42Val Uncertain significance ★ ⚠ same condition
KRT16 p.Ala433Thr Uncertain significance ★ ⚠ same condition
KRT16 p.Ala61Val Uncertain significance ★ ⚠ 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/krt16-p-asp110val (accessed [today's date]).

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