Is EFHD1 p.Ser201Leu (c.602C>T) pathogenic?

EFHD1 p.Ser201Leu (c.602C>T) is classified Uncertain significance in EFHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.00878%, sas).

How common is EFHD1 p.Ser201Leu (c.602C>T) in the general population?

EFHD1 p.Ser201Leu (c.602C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about EFHD1 p.Ser201Leu (c.602C>T)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

EFHD1 p.Ser201Leu

c.602C>T · VCV4247095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.82	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 0.19	GERP -3.4, phastCons 0.003
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.33 · regional, not allelic
Overall
CADD	8.028	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 0.00878% South Asian · 8/91,068 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00384% 62/1,614,118 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
African / African-American	0.00666%	15,012
Remaining individualsnot grpmax-eligible	0.0048%	20,834
European (non-Finnish)	0.0039%	25,652

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: EFHD1
Protein: p.Ser201Leu
Coding: c.602C>T
MANE Select: NM_025202
Type: single nucleotide variant
Location: chr2:232681601 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.10
Residue 201: a modified residue (phosphoserine)

Full EFHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFHD1 p.Ala124Thr Uncertain significance ★ ⚠ same type
EFHD1 p.Ala159Val Uncertain significance ★ ⚠ same type
EFHD1 p.Ala19Asp Uncertain significance ★ ⚠ same type
EFHD1 p.Ala49Pro Uncertain significance ★ ⚠ same type
EFHD1 p.Arg13Trp Uncertain significance ★ ⚠ same type
EFHD1 p.Arg149Gln Uncertain significance ★ ⚠ same type
EFHD1 p.Arg218Trp Uncertain significance ★ ⚠ same type
EFHD1 p.Arg224Gly 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/efhd1-p-ser201leu (accessed [today's date]).

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