Is KRT16 p.Ala249= (c.747C>T) pathogenic?

KRT16 p.Ala249= (c.747C>T) is classified Likely benign in KRT16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-06). Very rare (popmax 0.0022%, sas).

How common is KRT16 p.Ala249= (c.747C>T) in the general population?

KRT16 p.Ala249= (c.747C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

KRT16 p.Ala249=

c.747C>T · VCV3712132

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 1.8, phastCons 1
Overall
CADD	11.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.00031% 5/1,614,168 alleles · very rare exomes 5/1,461,842 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
South Asiangrpmax	0.0022%	45,543
European (non-Finnish)	0.000169%	590,005

Ashkenazi Jewish 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.Ala249=
Coding: c.747C>T
MANE Select: NM_005557
Type: single nucleotide variant
Location: chr17:41611369 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.26
Residue 249: the if rod domain; the 'coil 1b' region

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

Similar variants

KRT16 p.Ala249Val Likely benign ★ same residue
KRT16 p.Arg127Cys Pathogenic ★★ same type
KRT16 p.Arg127Gly Pathogenic ★★ same type
KRT16 p.Asn125Ser Pathogenic ★★ same type
KRT16 p.Leu124His Pathogenic/Likely pathogenic ★★ same type
KRT16 p.Met121Thr Pathogenic/Likely pathogenic ★★ same type
KRT16 p.Arg290His Uncertain significance ★★ ⚠ same type
KRT16 p.Glu442Lys 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/krt16-p-ala249 (accessed [today's date]).

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